Abstract
Protein structure refinement refers to the process of improving the qualities of protein structures during structure modeling processes to bring them closer to their native states. Structure refinement has been drawing increasing attention in the community-wide Critical Assessment of techniques for Protein Structure prediction (CASP) experiments since its addition in 8th CASP experiment. During the 9th and recently concluded 10th CASP experiments, a consistent growth in number of refinement targets and participating groups has been witnessed. Yet, protein structure refinement still remains a largely unsolved problem with majority of participating groups in CASP refinement category failed to consistently improve the quality of structures issued for refinement. In order to alleviate this need, we developed a completely automated and computationally efficient protein 3D structure refinement method, i3Drefine, based on an iterative and highly convergent energy minimization algorithm with a powerful all-atom composite physics and knowledge-based force fields and hydrogen bonding (HB) network optimization technique. In the recent community-wide blind experiment, CASP10, i3Drefine (as ‘MULTICOM-CONSTRUCT’) was ranked as the best method in the server section as per the official assessment of CASP10 experiment. Here we provide the community with free access to i3Drefine software and systematically analyse the performance of i3Drefine in strict blind mode on the refinement targets issued in CASP10 refinement category and compare with other state-of-the-art refinement methods participating in CASP10. Our analysis demonstrates that i3Drefine is only fully-automated server participating in CASP10 exhibiting consistent improvement over the initial structures in both global and local structural quality metrics. Executable version of i3Drefine is freely available at http://protein.rnet.missouri.edu/i3drefine/.
Highlights
The biennial community-wide Critical Assessment of protein Structure Prediction (CASP) experiment aims to evaluate the progress and challenges in the state-of-the-art of protein structure modeling techniques, one of the fundamental problems in computational biology- prediction of the tertiary structure of protein from its sequence information
The contribution of this article are two-fold: (1) Providing the community with access to a fast, accurate and freely downloadable executable version of refinement software which could be used to improve the qualities of the models coming from variety of protein structure prediction methods, or to act as the end-game strategy in a template-based modeling (TBM) pipeline and (2) evaluation of its performance in CASP10 refinement experiment to analyse the effectiveness of this method in a strict blind mode
The fully automated i3Drefine software was first blindly tested in CASP10 refinement experiment, 2012 with the group name MULTICOM-CONSTRUCT (Server group 222)
Summary
The biennial community-wide Critical Assessment of protein Structure Prediction (CASP) experiment aims to evaluate the progress and challenges in the state-of-the-art of protein structure modeling techniques, one of the fundamental problems in computational biology- prediction of the tertiary structure of protein from its sequence information. Structure refinement has proven to extremely challenging as revealed in the assessment of refinement experiments during CASP8 and CASP9 [9,10] with only a few participating groups were able to improve the model quality consistently It should be noted, that CASP refinement category differs in a slight but significant way from refinement in the context of TBM [11,12,13,14,15,16,17,18,19] where the objective is to refine the best identified template structure(s) to produce better quality prediction. In CASP, on the other hand, the starting models issued for refinement have already been refined by other structure
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