Conservation, Evolutionary: Difference between revisions

Patches of highly conserved amino acid residues on the surface of a protein molecular structure are good candidates for [[Site | functional sites]]. Every article in Proteopedia that is '''titled with a [[PDB code]]''' has an ''Evolutionary Conservation'' section below the molecular scene. Clicking '''show''' in the blue ''Evolutionary Conservation'' bar automatically colors all chain in the molecule by evolutionary conservation as calculated by [http://consurfdb.tau.ac.il ConSurfDB].

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 ConSurfDB] 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.

For example, consider [[1bqh]], which contains 10 chains, representing two copies of a 5-chain molecule. Each molecule contains four sequence-different chains. A visit to [http://consurfdb.tau.ac.il ConSurfDB] reveals, as expected, that a different number of sequences was utilized for the multiple sequence alignment (MSA) and conservation calculations for each of these sequence-different chains, and that each MSA had a different average pairwise difference (APD), a measure of diversity within the MSA. Therefore, residues with, for example, conservation level 9 (maximal conservation) in each of the three ConSurfDB-colored sequence-different chains have the highest levels of conservation within their own chain, but do not have exactly the same absolute levels of conservation.

In Proteopedia's ''Evolutionary Conservation'' scenes, we have chosen to color all the chains in the molecule at once. This gives a potentially useful overview, but can be misleading unless one realizes that a given conservation color, in two sequence-different chains, does not mean exactly the same level of conservation. In contrast to Proteopedia's ''Evolutionary Conservation'' scenes,  ConSurfDB and ConSurf Server apply conservation level colors to only one chain sequence at a time, thereby avoiding this possible confusion.

A second caveat bears mentioning here. Slight variations in the conservation pattern will occur over time, as the number of sequences in the sequence databases used by ConSurfDB increase. Each update of ConSurfDB uses somewhat larger sequence databases, and consequently, the MSA's for each chain will be slightly different.

==The ConSurfDB Mechanism==

The ConSurf DataBase server, [http://consurfdb.tau.ac.il ConSurfDB], pre-calculates conservation levels for each amino acid in every protein chain in the [[Protein Data Bank]].

<applet load='2vaa' size='400' frame='true' align='right' caption='Evolutionary conservation reported by ConSurfDB for Major Histocompatibility Class I alpha chain in [[2vaa]].' scene='Conservation,_Evolutionary/2vaa/1' />

At right is the pattern of evolutionary conservation and variability reported by [http://consurfdb.tau.ac.il ConSurfDB] for the alpha chain of [[Major Histocompatibility Complex Class I]] (chain A of [[2vaa]]).