TY - JOUR
T1 - Protein loop modeling with optimized backbone potential functions
AU - Liang, Shide
AU - Zhang, Chi
AU - Sarmiento, Jamica
AU - Standley, Daron M.
PY - 2012/5/8
Y1 - 2012/5/8
N2 - We represented protein backbone potential as a Fourier series. The parameters of the backbone dihedral potential were initialized to random values and optimized by Monte Carlo simulations so that generated native-like loop decoys had a lower energy than non-native decoys. The low energy regions of the optimized backbone potential were consistent with observed Ramachandran plots derived from crystal structures. The backbone potential was then used for the prediction of loop conformations (OSCAR-loop) combining with the previously described OSCAR force field, which has been shown to be very accurate in side chain modeling. As a result, the accuracy of OSCAR-loop was improved by local energy minimization based on the complete force field. The average accuracies were 0.40, 0.70, 1.10, 2.08, and 3.58 Å for 4, 6, 8, 10, and 12-residue loops, respectively, with each size being represented by 325 to 2809 targets. The accuracy was better than that of other loop modeling algorithms for short loops (<10 residues). For longer loops, the prediction accuracy was improved by concurrently sampling with a fragment-based method, Spanner. OSCAR-loop is available for download at http://sysimm.ifrec.osaka-u.ac.jp/OSCAR/.
AB - We represented protein backbone potential as a Fourier series. The parameters of the backbone dihedral potential were initialized to random values and optimized by Monte Carlo simulations so that generated native-like loop decoys had a lower energy than non-native decoys. The low energy regions of the optimized backbone potential were consistent with observed Ramachandran plots derived from crystal structures. The backbone potential was then used for the prediction of loop conformations (OSCAR-loop) combining with the previously described OSCAR force field, which has been shown to be very accurate in side chain modeling. As a result, the accuracy of OSCAR-loop was improved by local energy minimization based on the complete force field. The average accuracies were 0.40, 0.70, 1.10, 2.08, and 3.58 Å for 4, 6, 8, 10, and 12-residue loops, respectively, with each size being represented by 325 to 2809 targets. The accuracy was better than that of other loop modeling algorithms for short loops (<10 residues). For longer loops, the prediction accuracy was improved by concurrently sampling with a fragment-based method, Spanner. OSCAR-loop is available for download at http://sysimm.ifrec.osaka-u.ac.jp/OSCAR/.
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U2 - 10.1021/ct300131p
DO - 10.1021/ct300131p
M3 - Article
C2 - 26593673
AN - SCOPUS:84860711064
VL - 8
SP - 1820
EP - 1827
JO - Journal of Chemical Theory and Computation
JF - Journal of Chemical Theory and Computation
SN - 1549-9618
IS - 5
ER -