Prediction of Protein Tertiary Structure via Regularized Template Classification Techniques

Abstract

We discuss the use of the regularized linear discriminant analysis (LDA) as a model reduction technique combined with particle swarm optimization (PSO) in protein tertiary structure prediction, followed by structure refinement based on singular value decomposition (SVD) and PSO. The algorithm presented in this paper corresponds to the category of template-based modeling. The algorithm performs a preselection of protein templates before constructing a lower dimensional subspace via a regularized LDA. The protein coordinates in the reduced spaced are sampled using a highly explorative optimization algorithm, regressive–regressive PSO (RR-PSO). The obtained structure is then projected onto a reduced space via singular value decomposition and further optimized via RR-PSO to carry out a structure refinement. The final structures are similar to those predicted by best structure prediction tools, such as Rossetta and Zhang servers. The main advantage of our methodology is that alleviates the ill-posed character of protein structure prediction problems related to high dimensional optimization. It is also capable of sampling a wide range of conformational space due to the application of a regularized linear discriminant analysis, which allows us to expand the differences over a reduced basis set.