EXIA2: web server of accurate and rapid protein catalytic residue prediction.

Chih-Hao Lu,Yu-Tung Chien,Shao-Wei Huang,Chin-Sheng Yu

doi:10.1155/2014/807839

Abstract

We propose a method (EXIA2) of catalytic residue prediction based on protein structure without needing homology information. The method is based on the special side chain orientation of catalytic residues. We found that the side chain of catalytic residues usually points to the center of the catalytic site. The special orientation is usually observed in catalytic residues but not in noncatalytic residues, which usually have random side chain orientation. The method is shown to be the most accurate catalytic residue prediction method currently when combined with PSI-Blast sequence conservation. It performs better than other competing methods on several benchmark datasets that include over 1,200 enzyme structures. The areas under the ROC curve (AUC) on these benchmark datasets are in the range from 0.934 to 0.968.

Highlights

Enzymes play important roles in various biological processes
The results indicate that EXIA2, which uses side chain orientation and structure flexibility, is more effective than the structure features used by partial order optimum likelihood (POOL)
In addition to accurate identification of catalytic residues, the web server provides detailed scoring data, including the side chain orientation, structural flexibility, amino acid combination, and sequence conservation scores, for users to inspect and analyze the enzyme structure.The advantage of EXIA2 is that it does not rely on sequence or structure homology information

Summary

Introduction

Enzymes play important roles in various biological processes. As the number of sequenced genomes rapidly grows, the function of the majority of proteins can only be annotated computationally. To identify the location of functional regions in protein, a number of methods have been reported to predict protein functional site, including ligand binding sites [11,12,13], phosphorylation sites [14, 15], protein-protein interaction sites [16,17,18], and ubiquitination site [19] from protein sequence, structure, or high-throughput experimental data. Only a small number of residues compose enzyme catalytic site, they are the most crucial part for enzymes to perform their function. Identifying these critical residues and characterizing their features are crucial to understanding the molecular basis of protein function

Methods

Results

Conclusion