Modelling protein side-chain conformations using constraint logic programming

Abstract

Side-chain placement is an important sub-task in protein modelling. Selecting conformations for side-chains is a difficult problem because of the large search space to be explored. This problem can be addressed using constraint logic programming (CLP), which is an artificial intelligence technique developed to solve large combinatorial search problems. The side-chain placement problem can be expressed as a CLP program in which rotamer conformations are used as values for finite domain variables, and bad steric contacts involving rotamers are represented as constraints. This paper introduces the concept of null rotamers, and shows how these can be used in implementing a novel iterative approach. We present results that compare the accuracy of models constructed using different rotamer libraries and different domain variable enumeration heuristics. The results obtained using this CLP-based approach compare favourably with those obtained by other methods.