Protein loop modeling with optimized backbone potential functions

Shide Liang, Chi Zhang, Jamica Sarmiento, Daron M. Standley

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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/.

Original languageEnglish (US)
Pages (from-to)1820-1827
Number of pages8
JournalJournal of Chemical Theory and Computation
Volume8
Issue number5
DOIs
StatePublished - May 8 2012

Fingerprint

proteins
Proteins
Fourier series
Conformations
Crystal structure
Sampling
decoys
field theory (physics)
predictions
energy
plots
sampling
fragments
Monte Carlo simulation
crystal structure
optimization
simulation

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Computer Science Applications

Cite this

Protein loop modeling with optimized backbone potential functions. / Liang, Shide; Zhang, Chi; Sarmiento, Jamica; Standley, Daron M.

In: Journal of Chemical Theory and Computation, Vol. 8, No. 5, 08.05.2012, p. 1820-1827.

Research output: Contribution to journalArticle

Liang, Shide ; Zhang, Chi ; Sarmiento, Jamica ; Standley, Daron M. / Protein loop modeling with optimized backbone potential functions. In: Journal of Chemical Theory and Computation. 2012 ; Vol. 8, No. 5. pp. 1820-1827.
@article{4fe4944d8cea43efbc04e6b33214615b,
title = "Protein loop modeling with optimized backbone potential functions",
abstract = "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 {\AA} 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/.",
author = "Shide Liang and Chi Zhang and Jamica Sarmiento and Standley, {Daron M.}",
year = "2012",
month = "5",
day = "8",
doi = "10.1021/ct300131p",
language = "English (US)",
volume = "8",
pages = "1820--1827",
journal = "Journal of Chemical Theory and Computation",
issn = "1549-9618",
publisher = "American Chemical Society",
number = "5",

}

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/.

UR - http://www.scopus.com/inward/record.url?scp=84860711064&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860711064&partnerID=8YFLogxK

U2 - 10.1021/ct300131p

DO - 10.1021/ct300131p

M3 - Article

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 -