Improved Prediction of Protein Side-Chain Conformations With SCWRL4

Proteins. 2009 Dec;77(4):778-95. doi: 10.1002/prot.22488.

Abstract

Determination of side-chain conformations is an important step in protein structure prediction and protein design. Many such methods have been presented, although only a small number are in widespread use. SCWRL is one such method, and the SCWRL3 program (2003) has remained popular because of its speed, accuracy, and ease-of-use for the purpose of homology modeling. However, higher accuracy at comparable speed is desirable. This has been achieved in a new program SCWRL4 through: (1) a new backbone-dependent rotamer library based on kernel density estimates; (2) averaging over samples of conformations about the positions in the rotamer library; (3) a fast anisotropic hydrogen bonding function; (4) a short-range, soft van der Waals atom-atom interaction potential; (5) fast collision detection using k-discrete oriented polytopes; (6) a tree decomposition algorithm to solve the combinatorial problem; and (7) optimization of all parameters by determining the interaction graph within the crystal environment using symmetry operators of the crystallographic space group. Accuracies as a function of electron density of the side chains demonstrate that side chains with higher electron density are easier to predict than those with low-electron density and presumed conformational disorder. For a testing set of 379 proteins, 86% of chi(1) angles and 75% of chi(1+2) angles are predicted correctly within 40 degrees of the X-ray positions. Among side chains with higher electron density (25-100th percentile), these numbers rise to 89 and 80%. The new program maintains its simple command-line interface, designed for homology modeling, and is now available as a dynamic-linked library for incorporation into other software programs.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Computer Simulation
  • Crystallography, X-Ray
  • Hydrogen Bonding
  • Models, Molecular
  • Peptide Library
  • Protein Conformation*
  • Proteins / chemistry*
  • Sequence Alignment / statistics & numerical data
  • Software Design
  • Software*
  • Static Electricity
  • Thermodynamics

Substances

  • Peptide Library
  • Proteins