https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Mati+CohenProteopedia - User contributions [en]2026-09-16T05:08:51ZUser contributionsMediaWiki 1.43.8https://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837659Sandbox Mati2013-09-01T18:57:25Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene=''>Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/9'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/7'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hyd/4'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837658Sandbox Mati2013-09-01T18:54:45Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene=''>Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/7'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/7'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hyd/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837657Sandbox Mati2013-09-01T18:54:14Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene=''>Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/7'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/7'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hyd/3'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837656Sandbox Mati2013-09-01T18:47:59Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene=''>Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/7'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/7'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hyd/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837655Sandbox Mati2013-09-01T18:43:45Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene=''>Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/7'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/6'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hyd/1'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837654Sandbox Mati2013-09-01T18:40:20Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene=''>Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/6'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/5'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hyd/1'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837653Sandbox Mati2013-09-01T18:39:50Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene=''> <br />
<br />
Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/6'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/5'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hyd/1'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837652Sandbox Mati2013-09-01T18:39:21Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<br />
<br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene=''> <br />
<br />
Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/6'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/5'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hyd/1'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837650Sandbox Mati2013-09-01T12:29:51Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<br />
<br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene=''> <br />
<br />
Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837649Sandbox Mati2013-09-01T12:29:24Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<br />
<br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene=''> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837648Sandbox Mati2013-09-01T12:24:49Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<br />
<br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='' Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.></div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837647Sandbox Mati2013-09-01T12:23:40Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<br />
<br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='' Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity./></div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837646Sandbox Mati2013-09-01T12:23:19Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<br />
<br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene=''/> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837645Sandbox Mati2013-09-01T12:22:39Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<br />
<br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity./></div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837644Sandbox Mati2013-09-01T12:20:51Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<br />
<br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837643Sandbox Mati2013-09-01T12:19:10Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<br />
<br />
<StructureSection load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</StructureSection></div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837642Sandbox Mati2013-09-01T12:18:45Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<br />
<br />
<Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</StructureSection></div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837641Sandbox Mati2013-09-01T12:18:23Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<br />
<br />
<Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity. </StructureSection></div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837640Sandbox Mati2013-09-01T12:16:11Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <br />
<br />
<StructureSection load='1dq8' size='500' side='right' caption='Structure of HMG-CoA reductase (PDB entry [[1dq8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> <br />
<br />
Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837639Sandbox Mati2013-09-01T12:15:38Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <StructureSection load='1dq8' size='500' side='right' caption='Structure of HMG-CoA reductase (PDB entry [[1dq8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> <br />
<br />
Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837638Sandbox Mati2013-09-01T12:14:27Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface== <StructureSection load='1dq8' size='500' side='right' caption='Structure of HMG-CoA reductase (PDB entry [[1dq8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837637Sandbox Mati2013-09-01T12:14:12Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface == <StructureSection load='1dq8' size='500' side='right' caption='Structure of HMG-CoA reductase (PDB entry [[1dq8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837636Sandbox Mati2013-09-01T12:13:50Z<p>Mati Cohen: </p>
<hr />
<div>==Symmetry in the Bcl-Xl interface ==<StructureSection load='1dq8' size='500' side='right' caption='Structure of HMG-CoA reductase (PDB entry [[1dq8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837635Sandbox Mati2013-09-01T12:12:30Z<p>Mati Cohen: </p>
<hr />
<div>==Your Heading Here (maybe something like 'Structure')==<StructureSection load='1dq8' size='500' side='right' caption='Structure of HMG-CoA reductase (PDB entry [[1dq8]])' scene=''>Anything in this section will appear adjacent to the 3D structure and will be scrollable.</StructureSection><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837628Sandbox Mati2013-09-01T08:48:47Z<p>Mati Cohen: </p>
<hr />
<div><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [[1bxl]].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837627Sandbox Mati2013-09-01T08:48:08Z<p>Mati Cohen: </p>
<hr />
<div><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]] shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837626Sandbox Mati2013-09-01T08:47:49Z<p>Mati Cohen: </p>
<hr />
<div><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj]]shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837625Sandbox Mati2013-09-01T08:47:31Z<p>Mati Cohen: </p>
<hr />
<div><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [[2yxj 2yxj]]shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837622Sandbox Mati2013-09-01T08:14:22Z<p>Mati Cohen: </p>
<hr />
<div><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [http://www.proteopedia.org/wiki/index.php/2yxj 2yxj]shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/4'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837621Sandbox Mati2013-09-01T08:11:25Z<p>Mati Cohen: </p>
<hr />
<div><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [http://www.proteopedia.org/wiki/index.php/2yxj 2yxj]shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/2'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837620Sandbox Mati2013-09-01T08:09:51Z<p>Mati Cohen: </p>
<hr />
<div><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [http://www.proteopedia.org/wiki/index.php/2yxj 2yxj]shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/3'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/2'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/3'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=User:Mati_Cohen&diff=1837618User:Mati Cohen2013-09-01T08:00:20Z<p>Mati Cohen: </p>
<hr />
<div><br />
[[Image:Mati_Cohen.jpg|thumb|Mati Cohen]]<br />
Mati Cohen <br />
<br />
==Biography==<br />
Mati did his B.A at Bar Ilan University majored in Biology. M.Sc in Biology, at the Weizmann Institute of Science working on protein folding on the single molecule level. Mati got his PhD in biology developing both experimental and computational tools for de-novo interface design.<br />
Currently he is positioned as a Senior structure biologist at HQL pharmaceuticals. There he is designing templates for an efficient search of small molecule inhibitors for protein protein interaction.<br />
<br />
email: <email> mati@hql.co.il</email><br><br />
phone: 052-3772390<br></div>Mati Cohenhttps://proteopedia.org/index.php?title=User:Mati_Cohen&diff=1837617User:Mati Cohen2013-09-01T07:59:54Z<p>Mati Cohen: </p>
<hr />
<div><br />
<br />
[[Image:Mati_Cohen.jpg|thumb|Mati Cohen]]Mati Cohen<br />
Mati Cohen<br> <br />
email: <email> mati@hql.co.il</email><br><br />
phone: 052-3772390<br><br />
==Biography==<br />
Mati did his B.A at Bar Ilan University majored in Biology. M.Sc in Biology, at the Weizmann Institute of Science working on protein folding on the single molecule level. Mati got his PhD in biology developing both experimental and computational tools for de-novo interface design.<br />
Currently he is positioned as a Senior structure biologist at HQL pharmaceuticals. There he is designing templates for an efficient search of small molecule inhibitors for protein protein interaction.</div>Mati Cohenhttps://proteopedia.org/index.php?title=User:Mati_Cohen&diff=1837616User:Mati Cohen2013-09-01T07:59:29Z<p>Mati Cohen: </p>
<hr />
<div>Mati Cohen<br />
Mati Cohen<br> <br />
email: <email> mati@hql.co.il</email><br><br />
<br />
phone: 052-3772390<br><br />
<br />
[[Image:Mati_Cohen.jpg|thumb|Mati Cohen]]<br />
==Biography==<br />
Mati did his B.A at Bar Ilan University majored in Biology. M.Sc in Biology, at the Weizmann Institute of Science working on protein folding on the single molecule level. Mati got his PhD in biology developing both experimental and computational tools for de-novo interface design.<br />
Currently he is positioned as a Senior structure biologist at HQL pharmaceuticals. There he is designing templates for an efficient search of small molecule inhibitors for protein protein interaction.</div>Mati Cohenhttps://proteopedia.org/index.php?title=User:Mati_Cohen&diff=1837612User:Mati Cohen2013-09-01T07:51:39Z<p>Mati Cohen: </p>
<hr />
<div>Mati Cohen<br />
[[Image:Mati_Cohen.jpg|thumb|Mati Cohen]]<br />
==Biography==<br />
Mati did his B.A at Bar Ilan University majored in Biology. M.Sc in Biology, at the Weizmann Institute of Science working on protein folding on the single molecule level. Mati got his PhD in biology developing both experimental and computational tools for de-novo interface design.<br />
Currently he is positioned as a Senior structure biologist at HQL pharmaceuticals. There he is designing templates for an efficient search of small molecule inhibitors for protein protein interaction.</div>Mati Cohenhttps://proteopedia.org/index.php?title=User:Mati_Cohen&diff=1837611User:Mati Cohen2013-09-01T07:51:00Z<p>Mati Cohen: </p>
<hr />
<div>Mati Cohen<br />
[[Image:Mati_Cohen.jpg|thumb|Mati Cohen]]<br />
==Biography==<br />
Mati did his B.A at Bar Ilan University majored in Biology. M.Sc in Biology, at the Weizmann Institute of Science working on protein folding on the single molecule level. Mati got his PhD in biology developing both experimental and computational tools for de-novo interface design.<br />
Currently he is positioned as a Senior structure biologist at HQL pharmaceuticals. there he is designing templates for an efficient search of small molecule inhibitors for protein protein interaction.</div>Mati Cohenhttps://proteopedia.org/index.php?title=User:Mati_Cohen&diff=1837609User:Mati Cohen2013-09-01T07:50:36Z<p>Mati Cohen: </p>
<hr />
<div>Mati Cohen<br />
[[Image:Mati_Cohen.jpg|thumb|alt=A]]<br />
==Biography==<br />
Mati did his B.A at Bar Ilan University majored in Biology. M.Sc in Biology, at the Weizmann Institute of Science working on protein folding on the single molecule level. Mati got his PhD in biology developing both experimental and computational tools for de-novo interface design.<br />
Currently he is positioned as a Senior structure biologist at HQL pharmaceuticals. there he is designing templates for an efficient search of small molecule inhibitors for protein protein interaction.</div>Mati Cohenhttps://proteopedia.org/index.php?title=User:Mati_Cohen&diff=1837608User:Mati Cohen2013-09-01T07:50:13Z<p>Mati Cohen: </p>
<hr />
<div>Mati Cohen<br />
[[Image:Mati_Cohen.jpg|alt=A]]<br />
==Biography==<br />
Mati did his B.A at Bar Ilan University majored in Biology. M.Sc in Biology, at the Weizmann Institute of Science working on protein folding on the single molecule level. Mati got his PhD in biology developing both experimental and computational tools for de-novo interface design.<br />
Currently he is positioned as a Senior structure biologist at HQL pharmaceuticals. there he is designing templates for an efficient search of small molecule inhibitors for protein protein interaction.</div>Mati Cohenhttps://proteopedia.org/index.php?title=File:Mati_Cohen.jpg&diff=1837607File:Mati Cohen.jpg2013-09-01T07:48:01Z<p>Mati Cohen: </p>
<hr />
<div></div>Mati Cohenhttps://proteopedia.org/index.php?title=User:Mati_Cohen&diff=1837606User:Mati Cohen2013-09-01T07:47:35Z<p>Mati Cohen: </p>
<hr />
<div>Mati Cohen<br />
[[Image:Mati_Cohen.jpg]]<br />
==Biography==<br />
Mati did his B.A at Bar Ilan University majored in Biology. M.Sc in Biology, at the Weizmann Institute of Science working on protein folding on the single molecule level. Mati got his PhD in biology developing both experimental and computational tools for de-novo interface design.<br />
Currently he is positioned as a Senior structure biologist at HQL pharmaceuticals. there he is designing templates for an efficient search of small molecule inhibitors for protein protein interaction.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837601Sandbox Mati2013-08-31T19:31:20Z<p>Mati Cohen: </p>
<hr />
<div><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [http://www.proteopedia.org/wiki/index.php/2yxj 2yxj]shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/5'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/2'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/1'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/2'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837600Sandbox Mati2013-08-31T19:29:24Z<p>Mati Cohen: </p>
<hr />
<div><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [http://www.proteopedia.org/wiki/index.php/2yxj 2yxj]shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/4'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/2'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/1'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/2'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837525Sandbox Mati2013-08-28T19:37:31Z<p>Mati Cohen: </p>
<hr />
<div><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [http://www.proteopedia.org/wiki/index.php/2yxj 2yxj]shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/3'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/2'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/1'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. A look at the <scene name='43/437742/2yxj_space_fill_color_charged/2'>Overall</scene> picture shows that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837524Sandbox Mati2013-08-28T19:35:42Z<p>Mati Cohen: </p>
<hr />
<div><Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [http://www.proteopedia.org/wiki/index.php/2yxj 2yxj]shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/3'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/2'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/1'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. one can look at the <scene name='43/437742/2yxj_space_fill_color_charged/2'>Overall</scene> picture that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837523Sandbox Mati2013-08-28T19:34:49Z<p>Mati Cohen: </p>
<hr />
<div>Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family]. This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) <Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [http://www.proteopedia.org/wiki/index.php/2yxj 2yxj]shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/3'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/2'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/1'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. one can look at the <scene name='43/437742/2yxj_space_fill_color_charged/2'>Overall</scene> picture that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837522Sandbox Mati2013-08-28T19:23:57Z<p>Mati Cohen: </p>
<hr />
<div>Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family] .<br />
This family consists of [http://en.wikipedia.org/wiki/Apoptosis pro-apoptotic] and [http://en.wikipedia.org/wiki/Apoptosis anti-apoptotic] members. Bcl-Xl (in the image) <Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [http://www.proteopedia.org/wiki/index.php/2yxj 2yxj]shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/3'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/2'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/1'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. one can look at the <scene name='43/437742/2yxj_space_fill_color_charged/2'>Overall</scene> picture that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837521Sandbox Mati2013-08-28T19:21:17Z<p>Mati Cohen: </p>
<hr />
<div>Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family] .<br />
This family consists of pro-apoptotic and anti-apoptotic members. Bcl-Xl (in the image) <Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [http://www.proteopedia.org/wiki/index.php/2yxj 2yxj]shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl (Kd = 1nM). It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/3'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/2'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/1'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. one can look at the <scene name='43/437742/2yxj_space_fill_color_charged/2'>Overall</scene> picture that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837520Sandbox Mati2013-08-28T19:20:30Z<p>Mati Cohen: </p>
<hr />
<div>Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family] .<br />
This family consists of pro-apoptotic and anti-apoptotic members. Bcl-Xl (in the image) <Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> ,an anti-apoptotic protein, binds pro-apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [http://www.proteopedia.org/wiki/index.php/2yxj 2yxj]shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl Kd = 1nM. It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/3'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/2'>two negatively charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/1'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. one can look at the <scene name='43/437742/2yxj_space_fill_color_charged/2'>Overall</scene> picture that there are hydrophobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837497Sandbox Mati2013-08-28T11:13:47Z<p>Mati Cohen: </p>
<hr />
<div>Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family] .<br />
This family consists of pro-apoptotic and anti-apoptotic members. Bcl-Xl (in the image) <Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> ,an anti apoptotic protein, binds pro apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [http://www.proteopedia.org/wiki/index.php/2yxj 2yxj]shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl Kd = 1nM. It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/3'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/2'>two negativly charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/1'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. one can look at the <scene name='43/437742/2yxj_space_fill_color_charged/2'>Overall</scene> picture that there are hydropobic patches (in gray) "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohenhttps://proteopedia.org/index.php?title=Sandbox_Mati&diff=1837496Sandbox Mati2013-08-28T11:13:05Z<p>Mati Cohen: </p>
<hr />
<div>Bcl-Xl is a member of the [http://en.wikipedia.org/wiki/Bcl-2 Bcl-2 family] .<br />
This family consists of pro-apoptotic and anti-apoptotic members. Bcl-Xl (in the image) <Structure load='2yxj_With_Ligand_Mati_Cohen.pdb' size='500' frame='true' align='right' caption='Bcl-Xl and ABT737 from PDB-ID 2yxj' scene='Insert optional scene name here' /> ,an anti apoptotic protein, binds pro apoptotic proteins like BAK and BAD thus regularly inhibit program cell death. Many cancer cells overexpress at least one of the anti-apoptotic members of this family ,thus escaping a needed apoptosis . Therefore, these proteins are important targets for the development of new anti-cancer drugs.<br />
The PDB file [http://www.proteopedia.org/wiki/index.php/2yxj 2yxj]shows the structure of Bcl-Xl and ABT 737. ABT 737 is a potent inhibitor of Bcl-Xl Kd = 1nM. It binds Bcl-xl in the same position as BAK does as can be seen in [http://www.proteopedia.org/wiki/index.php/1bxl 1bxl].<br />
Interestingly the interface of Bcl-Xl is almost symmetric. There are <scene name='43/437742/2yxj_arg/3'>two positively charged residues</scene> Arg 100 and Arg 139.<br />
<scene name='43/437742/2yxj_glu/2'>two negativly charged residues</scene> Glu96 and Glu129.<br />
Two <scene name='43/437742/2yxj_hydrophobic/1'>hydrophobic patches</scene> which include Phe191 Val141 and <br />
Ala93 for one, and the other patch includes Phe146 Val126 and Leu108. one can look at the <scene name='43/437742/2yxj_space_fill_color_charged/2'>Overall</scene> picture that there are hydropobic patches "above" and "below" the ligand ,negatively charged residues "above-right" and "below-left" of the ligand and positively charges on the "right" and "left" of it.<br />
This symmetry can be exploited, a symmetric molecule can bind the same interface in two different ways thus increasing the "chance" of binding which means better binding affinity.</div>Mati Cohen