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A Practical Guide to Phylogenetics for Nonexperts
Published on: February 5, 2014
Evolutionary and structural feedback on selection of sequences for comparative analysis of proteins
I Mihalek1, I Res, O Lichtarge
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA. imihalek@bcm.tmc.edu
Proteins
|January 7, 2006
Summary
Slowly evolving protein residues cluster in native folds and indicate functional surfaces. This study shows these two properties are linked, meaning one implies the other for protein analysis.
Area of Science:
- Biochemistry
- Structural Biology
- Bioinformatics
Background:
- Slowly evolving protein residues exhibit two key traits: spatial clustering in the native protein fold and delineation of functional surfaces involved in molecular interactions.
- These functional surfaces mediate protein interactions with other proteins or small molecules.
Purpose of the Study:
- To demonstrate the strong coupling between residue clustering and functional surface delineation in proteins.
- To establish a method for selecting homologous sequences to optimize the detection of functional surfaces.
Main Methods:
- Utilized multiple sequence alignment (MSA) related methods with careful selection of relevant sequences.
- Applied the methods to two distinct protein datasets: a small set of diverse proteins and a large set of homodimerizing enzymes.
Main Results:
- Confirmed that the clustering of slowly evolving residues in the native fold statistically implies their role in delineating functional surfaces.
- Showcased that the coupling between these two properties is strong enough for one to predict the other.
Conclusions:
- A simple rule for selecting homologous sequences for comparative protein analysis is proposed: select sequences such that observed residues at any evolutionary divergence level cluster on the folded protein.
- This approach optimizes the detection of potentially unknown functional surfaces in proteins.
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