Title :
Residue-Specific Side-Chain Polymorphisms via Particle Belief Propagation
Author :
Soltan Ghoraie, Laleh ; Burkowski, Forbes ; Shuai Cheng Li ; Mu Zhu
Author_Institution :
Cheriton Sch. of Comput. Sci., Univ. of Waterloo, Waterloo, ON, Canada
Abstract :
Protein side chains populate diverse conformational ensembles in crystals. Despite much evidence that there is widespread conformational polymorphism in protein side chains, most of the X-ray crystallography data are modeled by single conformations in the Protein Data Bank. The ability to extract or to predict these conformational polymorphisms is of crucial importance, as it facilitates deeper understanding of protein dynamics and functionality. In this paper, we describe a computational strategy capable of predicting side-chain polymorphisms. Our approach extends a particular class of algorithms for side-chain prediction by modeling the side-chain dihedral angles more appropriately as continuous rather than discrete variables. Employing a new inferential technique known as particle belief propagation, we predict residue-specific distributions that encode information about side-chain polymorphisms. Our predicted polymorphisms are in relatively close agreement with results from a state-of-the-art approach based on X-ray crystallography data, which characterizes the conformational polymorphisms of side chains using electron density information, and has successfully discovered previously unmodeled conformations.
Keywords :
X-ray crystallography; biochemistry; bioinformatics; crystal structure; electron density; encoding; inference mechanisms; isomerism; learning (artificial intelligence); molecular biophysics; polymorphism; proteins; Protein Data Bank; X-ray crystallography data; computational strategy; conformational polymorphism extraction; conformational polymorphism prediction; continuous variables; crystal conformational ensembles; discrete variables; electron density information; inferential technique; particle belief propagation; protein dynamics; protein functionality; protein side chains; residue-specific distributions; residue-specific side-chain polymorphisms; side-chain dihedral angle modeling; side-chain polymorphism information encoding; side-chain prediction algorithms; Approximation methods; Belief propagation; Bioinformatics; Computational modeling; Libraries; Optimization; Proteins; Conformational ensemble; conformational polymorphism; mixture distribution; particle belief propagation; side-chain prediction; von-Mises distribution;
Journal_Title :
Computational Biology and Bioinformatics, IEEE/ACM Transactions on
DOI :
10.1109/TCBB.2013.130