Table of Contents Author Guidelines Submit a Manuscript
Comparative and Functional Genomics
Volume 4 (2003), Issue 4, Pages 420-423
Conference Review

In Silico Identification of Functional Protein Interfaces

Department of Biochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel

Received 22 May 2003; Revised 3 June 2003; Accepted 3 June 2003

Copyright © 2003 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Proteins perform many of their biological roles through protein–protein, protein–DNA or protein–ligand interfaces. The identification of the amino acids comprising these interfaces often enhances our understanding of the biological function of the proteins. Many methods for the detection of functional interfaces have been developed, and large-scale analyses have provided assessments of their accuracy. Among them are those that consider the size of the protein interface, its amino acid composition and its physicochemical and geometrical properties. Other methods to this effect use statistical potential functions of pairwise interactions, and evolutionary information. The rationale of the evolutionary approach is that functional and structural constraints impose selective pressure; hence, biologically important interfaces often evolve at a slower pace than do other external regions of the protein. Recently, an algorithm, Rate4Site, and a web-server, ConSurf (, for the identification of functional interfaces based on the evolutionary relations among homologous proteins as reflected in phylogenetic trees, were developed in our laboratory. The explicit use of the tree topology and branch lengths makes the method remarkably accurate and sensitive. Here we demonstrate its potency in the identification of the functional interfaces of a hypothetical protein, the structure of which was determined as part of the international structural genomics effort. Finally, we propose to combine complementary procedures, in order to enhance the overall performance of methods for the identification of functional interfaces in proteins.