Computational methods for identification of functional residues in protein structures

Abstract

The recent accumulation of experimentally determined protein 3D structures combined with our ability to computationally model structure from amino acid sequence has resulted in an increased importance of structure-based methods for protein function prediction. Two types of methods for function prediction have been proposed: those that can accurately predict overall biochemical or biological roles of a protein and those that predict its functional residues. Here, we review approaches used for the computational identification of functional residues in protein structures and summarize their applications to a wide variety of problems in functional proteomics, such as the prediction of catalytic residues, post-translational modifications, or nucleic acid-binding sites. We examine four different problems in order to perform a comparison between several recently proposed methods and, finally, conclude by identifying limitations and future challenges in this field.