Improved prediction of protein side‐chain conformations with SCWRL4

2009/05/29 by Georgii G. Krivov, Maxim V. Shapovalov, Roland L. Dunbrack · 11 citations
Biochemistry, Genetics and Molecular Biology · Computer Science · Materials Science · #Computational Drug Discovery Methods #Enzyme Structure and Function #Protein Structure and Dynamics

paper · pdf · doi:10.1002/prot.22488

openalex publication_date 2009/05/29 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29

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.

Citations

• The penultimate rotamer library

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