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Volume 10, Issue 8 (Suppl)

J Proteomics Bioinform, an open access journal

ISSN: 0974-276X

Structural Biology 2017

September 18-20, 2017

International Conference on

Structural Biology

September 18-20, 2017 Zurich, Switzerland

Marie Chabbert, J Proteomics Bioinform 2017, 10:8(Suppl)

DOI: 10.4172/0974-276X-C1-0100

Functional divergence in protein families: A co-variation analysis

Marie Chabbert

University of Angers, France

Statement of the Problem:

Co-variations between positions in amultiple sequence alignment may reflect structural, functional,

and/or phylogenetic constraints. Numerous co-variation methods have been developed and may yield a wide variety of results.

However, few studies have been undertaken to determine co-variations methods adequate to gain information on functional

divergence within a protein family.

Methodology &Theoretical Orientation:

We explore co- variation methods for their capability to mine co-varying positions

related to the functional divergence in a protein family. To reach this objective, we compare several methods on a model system

that consists of three nested sets of about 300, 100, and 20 paralogous sequences of a protein family, the class A of G protein-

coupled receptors. The co- variation methods analyzed are based on chi2 scores, mutual information, substitution matrices, or

perturbation methods. We analyze the dependence of the co-variation scores on residue conservation, measured by sequence

entropy, and the networking structure of the top pairs.

Findings:

Out of the four methods that privilege top pairs with intermediate entropy, two favor individual pairs, whereas the

other two methods, OMES (Observed minus Expected Squared) and ELSC (Explicit Likelihood of Subset Covariation), favor a

network structure with a central residue involved in several high scoring pairs. This network structure is observed for the three

sequence sets, making a hierarchical analysis possible. In each case, the central residue corresponds to a residue known to be

crucial for the evolution of the protein family and the sub-family specificity. Positions co-varying with this central residue form

a few clusters in the receptor 3D structure.

Conclusion & Significance:

The central residues obtained with the OMES or ELSC methods can be viewed as evolutionary

hubs, in relation with an epistasis-based mechanism of functional divergence within a protein family.

Biography

Marie Chabbert is a Scientist from the French CNRS (Centre National de la Recherche Scientifique). She has her expertise in molecular modeling and bioinformatics

approaches to the structure-function relationship of proteins. She has special interest in deciphering the mechanisms that drove protein evolution and in using

evolutionary data to gain structural and functional information on protein families. She is presently working on the G protein-coupled receptors, especially chemotaxis

and vasoactive peptide receptors.

marie.chabbert@univ-angers.fr

Figure1:

Visualization of co-varying residues in set

1 (a), 2 (b) and 3 (c) on the 3D structure of typical

G protein coupled receptors. The color code, from

yellow to red, is indicative of the co-variation score

with the central residue of the network.