Biological Sequence Analysis
ISIS: interaction sites identified from sequence
1 CUBIC & North-East Structural Genomics Consortium, Department of Biochemistry and Molecular Biophysics, Columbia University 630 West 168th Street, New York, NY 10032, USA
2 Columbia University Center for Computational Biology and Bioinformatics (C2B2), 1130 St Nicholas Avenue Rm 801, New York, NY 10032, USA
*To whom correspondence should be addressed.
 |
Abstract |
|---|
Motivation: Large-scale experiments reveal pairs of interacting proteins but leave the residues involved in the interactions unknown. These interface residues are essential for understanding the mechanism of interaction and are often desired drug targets. Reliable identification of residues that reside in protein–protein interface typically requires analysis of protein structure. Therefore, for the vast majority of proteins, for which there is no high-resolution structure, there is no effective way of identifying interface residues.
Results: Here we present a machine learning-based method that identifies interacting residues from sequence alone. Although the method is developed using transient protein–protein interfaces from complexes of experimentally known 3D structures, it never explicitly uses 3D information. Instead, we combine predicted structural features with evolutionary information. The strongest predictions of the method reached over 90% accuracy in a cross-validation experiment. Our results suggest that despite the significant diversity in the nature of protein–protein interactions, they all share common basic principles and that these principles are identifiable from sequence alone.
Contact: yanay.ofran{at}columbia.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Bromberg and B. Rost Comprehensive in silico mutagenesis highlights functionally important residues in proteins Bioinformatics, August 15, 2008; 24(16): i207 - i212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-R. Tang, Z.-Y. Sheng, Y.-Z. Chen, and Z. Zhang An improved prediction of catalytic residues in enzyme structures Protein Eng. Des. Sel., May 1, 2008; 21(5): 295 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Bromberg and B. Rost SNAP: predict effect of non-synonymous polymorphisms on function Nucleic Acids Res., June 28, 2007; 35(11): 3823 - 3835. [Abstract] [Full Text] [PDF]
|
|