Improving the accuracy of template-based predictions by mixing and matching between initial models

Our method takes into account the information presented in multiple templates/alignments at the three-dimensional level by mixing and matching regions between different initial comparative models. This method enables us to obtain an optimized conformation ensemble representing the best combination of secondary structures, resulting in the refined models of higher quality. In addition, the process of mixing and matching accumulates near-native conformations, resulting in discriminating the native-like conformation in a more effective manner. In the seventh Critical Assessment of Structure Prediction (CASP7) experiment, the refined models produced are more accurate than the starting initial models.This novel approach can be applied without any manual intervention to improve the quality of comparative predictions where multiple template/alignment combinations are available for modeling, producing conformational models of higher quality than the starting initial predictions.Comparative modeling methods are based on the observation that proteins related by evolution generally share similar three dimensional (3D) structures [1,2]. Therefore, the 3D models of a protein without an experimentally determined structure (target) can be built using alignments of the target sequence to one or more proteins with experimentally determined structures (templates). Currently, it is the most accurate approach for protein structure prediction, although there are significant bottlenecks that need to be overcome before models comparable to experimental results can be produced generally [3-5]. First, the accuracy of comparative predictions depends on the quality of the sequence alignments between the target and the templates sequences [1,2]. The results from the sixth Critical Assessment of Structure Prediction (CASP6) experiment indicates that even though there has been substantial progress in the quality of alignments, it has not resulted in an obvious improvement in the quality of the f