Improvement in low-homology template-based modeling by employing a model evaluation method with focus on topology

PLoS One. 2014 Feb 26;9(2):e89935. doi: 10.1371/journal.pone.0089935. eCollection 2014.

Abstract

Many template-based modeling (TBM) methods have been developed over the recent years that allow for protein structure prediction and for the study of structure-function relationships for proteins. One major problem all TBM algorithms face, however, is their unsatisfactory performance when proteins under consideration are low-homology. To improve the performance of TBM methods for such targets, a novel model evaluation method was developed here, and named MEFTop. Our novel method focuses on evaluating the topology by using two novel groups of features. These novel features included secondary structure element (SSE) contact information and 3-dimensional topology information. By combining MEFTop algorithm with FR-t5, a threading program developed by our group, we found that this modified TBM program, which was named FR-t5-M, exhibited significant improvements in predictive abilities for low-homology protein targets. We further showed that the MEFTop could be a generalized method to improve threading programs for low-homology protein targets. The softwares (FR-t5-M and MEFTop) are available to non-commercial users at our website: http://jianglab.ibp.ac.cn/lims/FRt5M/FRt5M.html.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Models, Molecular*
  • Protein Conformation
  • Proteins / chemistry*
  • Software*
  • Structural Homology, Protein*

Substances

  • Proteins

Grants and funding

This study was supported by Project 973 (2009CB918503), National Natural Science Foundation of China (31371338), Major National earmark Project for Infectious Diseases (2013ZX10004611-002) to TJ and National Natural Science Foundation of China (31100950) to AW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.