ConSurfDB vs. ConSurf: Difference between revisions

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#Upload each domain's PDB file to ConSurf as a separate job.
#Upload each domain's PDB file to ConSurf as a separate job.
</blockquote>
</blockquote>
==Examples==
<StructureSection load='' size='350' side='right' caption='' scene='39/399854/2vaa_consurf_halos_w274_y159/4'>
With default parameters, the ConSurf Server results have an average [[#Average Pairwise Distance]] (APD) of 1.00<ref name="APD">Tested with 20 arbitrarily selected proteins, mostly enzymes. Average of the average pairwise distance (APD) values: 1.00; range 0.82-1.42.</ref>, and an average of only a few "yellow" residues with insufficient data.<ref name="ISD">Tested with 20 arbitrarily selected proteins, mostly enzymes. Average number of amino acids with insufficient data ("yellow" in ConSurf): 3.5; range 0 to 16.</ref>
===Case #1: MHC===
The alpha chain of [https://www.youtube.com/watch?v=2ZakngfbHSo Major Histocompatibility Complex (MHC)] Class I protein has a groove that binds a wide range of peptides, and a small loop that binds CD8. Our example is [[2vaa]] (mouse H-2Kb).
<span style="float:right;">{{Template:ColorKey_ConSurf}}</span>
[[2vaa]] contains three chains. Here, (<scene name='39/399854/2vaa_consurf_halos_w274_y159/4'>restore initial scene, ConSurf Server default settings, APD 1.1</scene>) ConSurf colors are applied only to the alpha chain (chain A), while the beta chain (chain B = &beta;-2 microglobulin) and the 8 amino acid peptide (chain P) are shown as gray backbone traces.
Conservation of important residues in the groove is obscured by inclusion in the MSA of proteins with different functions ([[#Example With Multiple Functions|see analysis above]]). The sides of the groove are variable, as expected (enabling it to bind a wide range of peptide sequences). The only groove residue that is conserved at greater than level 7 is '''Tyr159''' (level 8), whose sidechain hydrogen bonds the main-chain oxygen of the amino-terminal peptide residue. Only a handful of surface residues are highly conserved (level 9), including '''Trp274''' involved in binding CD8.
See also [[Help:How to Insert a ConSurf Result Into a Proteopedia Green Link|How to Insert a ConSurf Result Into a Proteopedia Green Link]].
====ConSurfDB====
ConSurfDB has a result (NOT SHOWN) with an '''APD of 1.63''', much higher than the APD 1.1 for the ConSurf Server with default settings. As expected, nothing in the contacts between the peptide and the groove shows high conservation in the ConSurfDB result, but Trp274 (the CD8 binding site) remains highly conserved.
<font color="red">UPDATE IN PROGRESS:</FONT> [[User:Eric Martz|Eric Martz]] 15:02, 29 July 2024 (UTC)
Examples of conserved patches on other proteins, revealed by ConSurf, will be found in the articles on
*[[Lac repressor]]
*[[Avian Influenza Neuraminidase, Tamiflu and Relenza]]
*[[Mechanosensitive channels: opening and closing]]
</StructureSection>


==The ConSurf-DB Mechanism==
==The ConSurf-DB Mechanism==
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# Calculates a conservation score with confidence interval for each amino acid. Classifies the conservation scores into nine levels, and maps them to standard conservation level colors (see color key at the top of this page). Marks residues for which the conservation score confidence interval is too large, hence the conservation score is unreliable ("insufficient data").
# Calculates a conservation score with confidence interval for each amino acid. Classifies the conservation scores into nine levels, and maps them to standard conservation level colors (see color key at the top of this page). Marks residues for which the conservation score confidence interval is too large, hence the conservation score is unreliable ("insufficient data").
# Displays the protein, colored by conservation, in interactive 3D, using the NGL Viewer, [[FirstGlance in Jmol]], [[Chimera]], or [[PyMOL]].
# Displays the protein, colored by conservation, in interactive 3D, using the NGL Viewer, [[FirstGlance in Jmol]], [[Chimera]], or [[PyMOL]].
==Examples==
<StructureSection load='' size='350' side='right' caption='' scene='39/399854/2vaa_consurf_halos_w274_y159/4'>
With default parameters, the ConSurf Server results have an average [[#Average Pairwise Distance]] (APD) of 1.00<ref name="APD">Tested with 20 arbitrarily selected proteins, mostly enzymes. Average of the average pairwise distance (APD) values: 1.00; range 0.82-1.42.</ref>, and an average of only a few "yellow" residues with insufficient data.<ref name="ISD">Tested with 20 arbitrarily selected proteins, mostly enzymes. Average number of amino acids with insufficient data ("yellow" in ConSurf): 3.5; range 0 to 16.</ref>
===Case #1: MHC===
The alpha chain of [https://www.youtube.com/watch?v=2ZakngfbHSo Major Histocompatibility Complex (MHC)] Class I protein has a groove that binds a wide range of peptides, and a small loop that binds CD8. Our example is [[2vaa]] (mouse H-2Kb).
<span style="float:right;">{{Template:ColorKey_ConSurf}}</span>
[[2vaa]] contains three chains. Here, (<scene name='39/399854/2vaa_consurf_halos_w274_y159/4'>restore initial scene, ConSurf Server default settings, APD 1.1</scene>) ConSurf colors are applied only to the alpha chain (chain A), while the beta chain (chain B = &beta;-2 microglobulin) and the 8 amino acid peptide (chain P) are shown as gray backbone traces.
Conservation of important residues in the groove is obscured by inclusion in the MSA of proteins with different functions ([[#Example With Multiple Functions|see analysis above]]). The sides of the groove are variable, as expected (enabling it to bind a wide range of peptide sequences). The only groove residue that is conserved at greater than level 7 is '''Tyr159''' (level 8), whose sidechain hydrogen bonds the main-chain oxygen of the amino-terminal peptide residue. Only a handful of surface residues are highly conserved (level 9), including '''Trp274''' involved in binding CD8.
See also [[Help:How to Insert a ConSurf Result Into a Proteopedia Green Link|How to Insert a ConSurf Result Into a Proteopedia Green Link]].
====ConSurfDB====
ConSurfDB has a result (NOT SHOWN) with an '''APD of 1.63''', much higher than the APD 1.1 for the ConSurf Server with default settings. As expected, nothing in the contacts between the peptide and the groove shows high conservation in the ConSurfDB result, but Trp274 (the CD8 binding site) remains highly conserved.
<font color="red">UPDATE IN PROGRESS:</FONT> [[User:Eric Martz|Eric Martz]] 21:24, 23 July 2024 (UTC)
Examples of conserved patches on other proteins, revealed by ConSurf, will be found in the articles on
*[[Lac repressor]]
*[[Avian Influenza Neuraminidase, Tamiflu and Relenza]]
*[[Mechanosensitive channels: opening and closing]]
</StructureSection>


==References==
==References==
  {{Reflist}}
  {{Reflist}}
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