Protein NMR structures refined without NOE data

PLoS One. 2014 Oct 3;9(10):e108888. doi: 10.1371/journal.pone.0108888. eCollection 2014.

Abstract

The refinement of low-quality structures is an important challenge in protein structure prediction. Many studies have been conducted on protein structure refinement; the refinement of structures derived from NMR spectroscopy has been especially intensively studied. In this study, we generated flat-bottom distance potential instead of NOE data because NOE data have ambiguity and uncertainty. The potential was derived from distance information from given structures and prevented structural dislocation during the refinement process. A simulated annealing protocol was used to minimize the potential energy of the structure. The protocol was tested on 134 NMR structures in the Protein Data Bank (PDB) that also have X-ray structures. Among them, 50 structures were used as a training set to find the optimal "width" parameter in the flat-bottom distance potential functions. In the validation set (the other 84 structures), most of the 12 quality assessment scores of the refined structures were significantly improved (total score increased from 1.215 to 2.044). Moreover, the secondary structure similarity of the refined structure was improved over that of the original structure. Finally, we demonstrate that the combination of two energy potentials, statistical torsion angle potential (STAP) and the flat-bottom distance potential, can drive the refinement of NMR structures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Databases, Protein
  • Magnetic Resonance Spectroscopy / methods*
  • Models, Molecular*
  • Protein Conformation*
  • Proteins / chemistry*

Substances

  • Proteins

Grant support

This study was supported by grants from the Korean Research Institute of Bioscience and Biotechnology Research Initiative Program. The Korean Ministry of Education, Science and Technology (MEST) under grant numbers 2012R1A1A2002676, 2012-0006002, and 20120006011. The Pioneer Research Center Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (2013M3C1A3064780). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.