LEAP highly accurate prediction of protein loop conformations by integrating coarse-grained sampling and optimized energy scores with all-atom refinement of backbone and side chains

LEAP : highly accurate prediction of protein loop conformations by integrating coarse-grained sampling and optimized energy scores with all-atom refinement of backbone and side chains

Copyright © 2013 Wiley Periodicals, Inc.

Bibliographische Detailangaben
Veröffentlicht in:Journal of computational chemistry. - 1984. - 35(2014), 4 vom: 05. Feb., Seite 335-41
1. Verfasser: Liang, Shide (VerfasserIn)
Weitere Verfasser: Zhang, Chi, Zhou, Yaoqi
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2014
Zugriff auf das übergeordnete Werk:Journal of computational chemistry
Schlagworte:Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't loop modeling • coarse-grained energy function • energy minimization • Monte Carlo simulation • force field development Proteins
Beschreibung
Zusammenfassung:Copyright © 2013 Wiley Periodicals, Inc.
Prediction of protein loop conformations without any prior knowledge (ab initio prediction) is an unsolved problem. Its solution will significantly impact protein homology and template-based modeling as well as ab initio protein-structure prediction. Here, we developed a coarse-grained, optimized scoring function for initial sampling and ranking of loop decoys. The resulting decoys are then further optimized in backbone and side-chain conformations and ranked by all-atom energy scoring functions. The final integrated technique called loop prediction by energy-assisted protocol achieved a median value of 2.1 Å root mean square deviation (RMSD) for 325 12-residue test loops and 2.0 Å RMSD for 45 12-residue loops from critical assessment of structure-prediction techniques (CASP) 10 target proteins with native core structures (backbone and side chains). If all side-chain conformations in protein cores were predicted in the absence of the target loop, loop-prediction accuracy only reduces slightly (0.2 Å difference in RMSD for 12-residue loops in the CASP target proteins). The accuracy obtained is about 1 Å RMSD or more improvement over other methods we tested. The executable file for a Linux system is freely available for academic users at http://sparks-lab.org
Beschreibung:Date Completed 30.09.2014
Date Revised 10.11.2023
published: Print-Electronic
Citation Status MEDLINE
ISSN:1096-987X
DOI:10.1002/jcc.23509