A conformation ensemble approach to protein residue-residue contact

Jesse Eickholt,Zheng Wang,Jianlin Cheng

doi:10.1186/1472-6807-11-38

Abstract

BackgroundProtein residue-residue contact prediction is important for protein model generation and model evaluation. Here we develop a conformation ensemble approach to improve residue-residue contact prediction. We collect a number of structural models stemming from a variety of methods and implementations. The various models capture slightly different conformations and contain complementary information which can be pooled together to capture recurrent, and therefore more likely, residue-residue contacts.ResultsWe applied our conformation ensemble approach to free modeling targets from both CASP8 and CASP9. Given a diverse ensemble of models, the method is able to achieve accuracies of. 48 for the top L/5 medium range contacts and. 36 for the top L/5 long range contacts for CASP8 targets (L being the target domain length). When applied to targets from CASP9, the accuracies of the top L/5 medium and long range contact predictions were. 34 and. 30 respectively.ConclusionsWhen operating on a moderately diverse ensemble of models, the conformation ensemble approach is an effective means to identify medium and long range residue-residue contacts. An immediate benefit of the method is that when tied with a scoring scheme, it can be used to successfully rank models.

Highlights

Protein residue-residue contact prediction is important for protein model generation and model evaluation
When evaluating the method on the CASP8 and CASP9 free modeling (FM) targets, we find that it outperforms current approaches substantially and achieves long range contact accuracies of 36% on the CASP8 FM targets and 30% on the CASP9 FM targets
Datasets and Evaluation Metrics The prediction targets used in our study were the protein domains classified as free modeling (FM) targets for CASP8 and CASP9

Summary

Introduction

Protein residue-residue contact prediction is important for protein model generation and model evaluation. Even after many years of intense attention and development, de novo protein structure prediction remains a difficult and open problem. In part, this is due to the inadequacy of current de novo sampling techniques which are incapable of guiding the folding process through such a vast conformational space [1,2,3]. Given the importance and applicability of protein contacts, considerable effort has been put forth to develop methods which can predict protein residue-residue contacts. The majority of these methods can be categorized from 3D structural models generated for a protein. This approach has been used by the CASP assessors [25,26], a few CASP predictors such as SMEG-CCP (see CASP8 abstracts), and in scoring protein models [8]

Methods

Results

Conclusion