Template Scoring Methods for Protein Torsion Angle Prediction

Abstract

Prediction of backbone torsion angles provides important constraints about the 3D structure of a protein and is receiving a growing interest in the structure prediction community. In this paper, we introduce a three-stage machine learning classifier to predict the 7-state torsion angles of a protein. The first two stages employ dynamic Bayesian and neural networks to produce an ab-initio prediction of torsion angle states starting from sequence profiles. The third stage is a committee classifier, which combines the ab-initio prediction with a structural frequency profile derived from templates obtained by HHsearch. We develop several structural profile models and obtain significant improvements over the Laplacian scoring technique through: (1) scaling templates by integer powers of sequence identity score, (2) incorporating other alignment scores as multiplicative factors (3) adjusting or optimizing parameters of the profile models with respect to the similarity interval of the target. We also demonstrate that the torsion angle prediction accuracy improves at all levels of target-template similarity even when templates are distant from the target. The improvement is at significantly higher rates as template structures gradually get closer to target.