Conservation, Evolutionary: Difference between revisions

For a more basic explanation of this subject, please see [[Introduction to Evolutionary Conservation]].

Proteopedia's evolutionary conservation colors are pre-calculated by [[ConSurfDB vs. ConSurf|ConSurf-DB]].

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| colspan="2" |<br><ul><li>'''''Insufficient Data''''' describes amino acids for which a meaningful conservation level could not be derived from the set of homologous sequences utilized. This occurs when the confidence interval for the calculated conservation level is too large. For more, see the [[ConSurfDB_vs._ConSurf#ConSurf-DB_Process|ConSurfDB Process]].

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For an example, show ''Evolutionary Conservation'' at [[1hgf]].

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==Locating Conserved Patches==

Briefly, ConSurf-DB gathers sequences similar to that of the protein in question, then constructs a multiple sequence alignment, and analyses it for sequence positions that are conserved (have lower than average differences between sequences) and that are variable (have higher than average differences between sequences). Each amino acid is assigned a conservation score and corresponding color in Proteopedia's interactive 3D molecular scene.

Charged residues are usually on the surfaces of folded proteins. If you see a highly conserved charged residue (''Arg, Asp, Glu, Lys''') on the surface, often it participates in a [[Salt bridges|salt bridge]]. Salt bridges help to stabilize protein folds, and hence the residues involved are often highly conserved. Example: Asp6 with Arg8 in [[1qdq]].

Remember that you can touch any residue with the mouse in the ''Evolutionary Conservation'' scene in Proteopedia (in Jmol), and its identity will be displayed after a few seconds. This works best with spinning turned off.

This caveat applies only to molecules that contain chains with different sequences. The conservation colors shown in Proteopedia's ''Evolutionary Conservation'' scenes do not indicate the same levels of conservation for chains of different sequences. This is because  [http://consurfdb.tau.ac.il ConSurf-DB] calculates conservation levels independently for each sequence-different chain, and the levels are relative to the multiple sequence alignment constructed for each sequence-independent chain.

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===INTREPID===

&quot;[http://phylogenomics.berkeley.edu/INTREPID/index.html INTREPID] is an information-theoretic approach for functional site identification that exploits the information in large diverse multiple sequence alignments. INTREPID gathers homologs for a sequence using PSI-BLAST and estimates a phylogenetic tree. It then uses Jensen-Shannon divergence to measure the information for each position in the sequence at each subtree node encountered on a traversal of the phylogeny, tracing a path from the root to the leaf corresponding to the sequence of interest. Positions that are conserved across the entire family receive stronger scores than those that only become conserved within more closely related subgroups. This tree traversal produces a phylogenomic conservation score for each position in the MSA. INTREPID uses information from sequence only, and can thus be used when knowledge of structure is not available.&quot; (Quoted from the [http://phylogenomics.berkeley.edu/INTREPID/index.html INTREPID website].)

Evidence is provided that INTREPID out-performs ConSurf for predicting catalytic residues.

===xProtCAS===

===siteFiNDER|3D===

[http://sitefinder3d.mbb.yale.edu/ siteFiNDER|3D] performs ''conserved functional group'' (CFG) analysis. "CFG Analysis is a general method for predicting the location of functionally important sites within a target protein structure. Like other available structure/sequence analysis techniques, CFG Analysis exploits the evolutionary relationships present across groups of homologous proteins to identify regions that are likely to be of functional significance. However, this technique is particularly useful for situations where other methods fail, for instance when only a few or highly similar homologues can be identified." As its name implies, CFG analysis attempts to identify groups of conserved amino acids that together represent a functional site. In this respect, it goes beyond most other evolutionary conservation servers, which stop at assigning a conservation value to each amino acid. See the [http://consurfdb.tau.ac.il/comparison.php comparison of siteFiNDER|3D with ConSurf for cytochrome c].

===HotPatch===

===Evolutionary Trace Viewer===

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Comment by [[User:Eric Martz]], March, 2009: From the information provided on the ETV website, I found it quite difficult to understand what the ETV is doing, or how to use the viewer. An explanation in simple terms for non-specialists would be very useful.

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===EVcouplings / EVfold===

*[[ConSurfDB vs. ConSurf]]: How the servers work and how to get optimal results from ConSurf.

*[[Help:How to Insert a ConSurf Result Into a Proteopedia Green Link]]

==References==

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