Algorithmic and Artificial Intelligence Methods for Protein Bioinformatics

Chapter 3

Identifying Calcium Binding Sites in Proteins

HUI LIU and HAI DENG

3.1 Introduction

The number of experimentally and computationally derived structural models available in databases has been steadily increasing with the emergence of structural genomics projects worldwide. One important problem in current biology and chemistry is to assign proteins with functions based on 3D structure. Calcium, one of the most important metals for life, is responsible for regulating many biological processes through its interactions with numerous calcium binding proteins in different biological environments [1, 2]. Identifying the calcium binding sites is not only critical for the study of individual proteins but also helpful for revealing the general factors involved in such as the mechanisms governing calcium binding affinity, metal selectivity, and calcium-induced conformation change [3]. Sites are defined by a 3D location and a local neighborhood with a common structural or functional role. Non-calcium-binding sites are locations where the function does not occur or a different function is present. According to structural features, calcium binding sites can be classified as continuous or discontinuous [4, 5]. Continuous calcium binding sites consist of amino acids adjacent in primary sequence, usually in a highly conserved loop flanked by the helix–loop–helix, whereas discontinuous calcium binding sites consist of residues that are spatially proximate in the folded structure but distant ...