proteins STRUCTURE O FUNCTION O BIOINFORMATICS Improved prediction of protein side-chain conformations with SCWRL4

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 χ1 angles and 75% of χ1+2 angles are predicted correctly within 40° 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. Proteins 2009. © 2009 Wiley‐Liss, Inc.

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