Refined template selection and combination algorithm significantly improves template-based modeling accuracy

Abstract

In contrast to ab-initio protein modeling methodologies, comparative modeling is considered as the most popular and reliable algorithm to model protein structure. However, the selection of the best set of templates is still a major challenge. An effective template-ranking algorithm is developed to efficiently select only the reliable hits for predicting the protein structures. The algorithm employs the pairwise as well as multiple sequence alignments of template hits to rank and select the best possible set of templates. It captures several key sequences and structural information of template hits and converts into scores to effectively rank them. This selected set of templates is used to model a target. Modeling accuracy of the algorithm is tested and evaluated on TBM-HA domain containing CASP8, CASP9 and CASP10 targets. On an average, this template ranking and selection algorithm improves GDT-TS, GDT-HA and TM_Score by 3.531, 4.814 and 0.022, respectively. Further, it has been shown that the inclusion of structurally similar templates with ample conformational diversity is crucial for the modeling algorithm to maximally as well as reliably span the target sequence and construct its near-native model. The optimal model sampling also holds the key to predict the best possible target structure.