Sandbox Reserved 1849: Difference between revisions

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ACE2 binds to the spike protein RBD using <scene name='10/1075251/Ace2_allbinding/3'>these residues</scene>. The minibinders are smaller than ACE2, but still form strong connections to the spike protein. This means the minibinders interact with the RBD residues more efficiently than ACE2 giving them a higher affinity for the spike protein <ref name="Longxing">PMID:32907861</ref>. AHB2 was designed to mimic ACE2 while making better use of the RBD residues giving it a higher affinity for the spike protein with an IC50 value of 15.5 nM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Ahb2_all/3'>AHB2 and RBD binding residues</scene>). LCB1 was designed from scratch to bind the most efficiently to the RBD residues giving it the highest affinity with the lowest IC50 value of 23.5 pM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Lcb1_binding_residues/3'>LCB1 and RBD binding residues</scene>). LCB3 was designed after LCB1 with the goal of making the minibinder even more efficient, however it ended up having a lower affinity than LCB1 with a higher IC50 value of 40.1 pM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Lcb3_all/2'>LCB3 and RBD binding residues</scene>).

The Glutamine-493 residue on the spike protein is an important residue in showing the differences in strength between ACE2 and the minibinders <ref name="Longxing">PMID:32907861</ref>. ACE2 does not make use of this residue when <scene name='10/1075250/Q493_ace2/12'>binding to the RBD</scene>. The nearest residues of ACE2, Gln35 and Lys31 do not form any interaction on Gln493 of the spike protein. The AHB2 minibinder, instead forms a <scene name='10/1075251/Q493-ahb2/1'>hydrogen bond</scene> on the Gln493 of the spike protein residue of the spike protein with its Glu41, increasing affinity to the spike protein. LCB1 forms <scene name='10/1075250/Q493_lcb1/9'>two hydrogen bonds</scene> on Gln493 of the spike protein using its Asp17 and Arg14 residues, giving it the highest affinity based on the Gln493 residue. However, these interactions are not required. LCB1 forms <scene name='10/1075251/Q493-lcb3/1'>no interactions</scene> with the Gln493 residue of the RDB previously mentioned, yet it still has a higher affinity to the RBD than AHB2.

The Glutamine-493 residue on the spike protein is an important residue in showing the differences in strength between ACE2 and the minibinders <ref name="Longxing">PMID:32907861</ref>. ACE2 does not make use of this residue when <scene name='10/1075250/Q493_ace2/12'>binding to the RBD</scene>. The nearest residues of ACE2, Gln35 and Lys31, do not form any interaction on Gln493 of the spike protein. The AHB2 minibinder, instead forms a <scene name='10/1075251/Q493-ahb2/1'>hydrogen bond</scene> on the Gln493 of the spike protein residue of the spike protein with its Glu41, increasing affinity to the spike protein. LCB1 forms <scene name='10/1075250/Q493_lcb1/9'>two hydrogen bonds</scene> on Gln493 of the spike protein using its Asp17 and Arg14 residues, giving it the highest affinity based on the Gln493 residue. However, these interactions are not required. LCB1 forms <scene name='10/1075251/Q493-lcb3/1'>no interactions</scene> with the Gln493 residue of the RDB previously mentioned, yet it still has a higher affinity to the RBD than AHB2.

Similarly, ACE2 forms a hydrogen bond with the Lys417 from its Asp30 residue. LCB1, however, forms two hydrogen bonds with both the Lys417 and Arg403 of the spike protein from its Asp30 residue. This is a very strong interaction, further contributing to the high affinity of LCB1 to the spike protein<ref name="Longxing">PMID:32907861</ref>.

Sandbox Reserved 1849: Difference between revisions

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 ACE2 binds to the spike protein RBD using <scene name='10/1075251/Ace2_allbinding/3'>these residues</scene>. The minibinders are smaller than ACE2, but still form strong connections to the spike protein. This means the minibinders interact with the RBD residues more efficiently than ACE2 giving them a higher affinity for the spike protein <ref name="Longxing">PMID:32907861</ref>. AHB2 was designed to mimic ACE2 while making better use of the RBD residues giving it a higher affinity for the spike protein with an IC<sub>50</sub> value of 15.5 nM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Ahb2_all/3'>AHB2 and RBD binding residues</scene>). LCB1 was designed from scratch to bind the most efficiently to the RBD residues giving it the highest affinity with the lowest IC<sub>50</sub> value of 23.5 pM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Lcb1_binding_residues/3'>LCB1 and RBD binding residues</scene>). LCB3 was designed after LCB1 with the goal of making the minibinder even more efficient, however it ended up having a lower affinity than LCB1 with a higher IC<sub>50</sub> value of 40.1 pM<ref name="Longxing">PMID:32907861</ref> (<scene name='10/1075251/Lcb3_all/2'>LCB3 and RBD binding residues</scene>).
-The Glutamine-493 residue on the spike protein is an important residue in showing the differences in strength between ACE2 and the minibinders <ref name="Longxing">PMID:32907861</ref>. ACE2 does not make use of this residue when <scene name='10/1075250/Q493_ace2/12'>binding to the RBD</scene>. The nearest residues of ACE2, Gln35 and Lys31 do not form any interaction on Gln493 of the spike protein. The AHB2 minibinder, instead forms a <scene name='10/1075251/Q493-ahb2/1'>hydrogen bond</scene> on the Gln493 of the spike protein residue of the spike protein with its Glu41, increasing affinity to the spike protein. LCB1 forms <scene name='10/1075250/Q493_lcb1/9'>two hydrogen bonds</scene> on Gln493 of the spike protein using its Asp17 and Arg14 residues, giving it the highest affinity based on the Gln493 residue. However, these interactions are not required. LCB1 forms <scene name='10/1075251/Q493-lcb3/1'>no interactions</scene> with the Gln493 residue of the RDB previously mentioned, yet it still has a higher affinity to the RBD than AHB2.
+The Glutamine-493 residue on the spike protein is an important residue in showing the differences in strength between ACE2 and the minibinders <ref name="Longxing">PMID:32907861</ref>. ACE2 does not make use of this residue when <scene name='10/1075250/Q493_ace2/12'>binding to the RBD</scene>. The nearest residues of ACE2, Gln35 and Lys31, do not form any interaction on Gln493 of the spike protein. The AHB2 minibinder, instead forms a <scene name='10/1075251/Q493-ahb2/1'>hydrogen bond</scene> on the Gln493 of the spike protein residue of the spike protein with its Glu41, increasing affinity to the spike protein. LCB1 forms <scene name='10/1075250/Q493_lcb1/9'>two hydrogen bonds</scene> on Gln493 of the spike protein using its Asp17 and Arg14 residues, giving it the highest affinity based on the Gln493 residue. However, these interactions are not required. LCB1 forms <scene name='10/1075251/Q493-lcb3/1'>no interactions</scene> with the Gln493 residue of the RDB previously mentioned, yet it still has a higher affinity to the RBD than AHB2.
 Similarly, ACE2 forms a hydrogen bond with the Lys417 from its Asp30 residue. LCB1, however, forms two hydrogen bonds with both the Lys417 and Arg403 of the spike protein from its Asp30 residue. This is a very strong interaction, further contributing to the high affinity of LCB1 to the spike protein<ref name="Longxing">PMID:32907861</ref>.