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 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.
Krivov
Georgii G
GG
Institute for Cancer Research, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111, USA.
Shapovalov
Maxim V
MV
Dunbrack
Roland L
RL
D000465:Algorithms; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D019151:Peptide Library; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment / Q000706:statistics & numerical data; D012984:Software; D012985:Software Design; D055672:Static Electricity; D013816:Thermodynamics
D019151:Peptide Library; D011506:Proteins