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Nucleic Acids Res. 2016 Jul 8;44(W1):W395-400. doi: 10.1093/nar/gkw395. Epub 2016 May 5.

RCD+: Fast loop modeling server.

Author information

1
Department of Biological Chemical Physics, Rocasolano Physical Chemistry Institute C.S.I.C., Serrano 119, 28006 Madrid, Spain.
2
Department of Computer Science, Old Dominion University, Norfolk, VA 23529, USA.
3
Department of Biological Chemical Physics, Rocasolano Physical Chemistry Institute C.S.I.C., Serrano 119, 28006 Madrid, Spain pablo@chaconlab.org.

Abstract

Modeling loops is a critical and challenging step in protein modeling and prediction. We have developed a quick online service (http://rcd.chaconlab.org) for ab initio loop modeling combining a coarse-grained conformational search with a full-atom refinement. Our original Random Coordinate Descent (RCD) loop closure algorithm has been greatly improved to enrich the sampling distribution towards near-native conformations. These improvements include a new workflow optimization, MPI-parallelization and fast backbone angle sampling based on neighbor-dependent Ramachandran probability distributions. The server starts by efficiently searching the vast conformational space from only the loop sequence information and the environment atomic coordinates. The generated closed loop models are subsequently ranked using a fast distance-orientation dependent energy filter. Top ranked loops are refined with the Rosetta energy function to obtain accurate all-atom predictions that can be interactively inspected in an user-friendly web interface. Using standard benchmarks, the average root mean squared deviation (RMSD) is 0.8 and 1.4 Å for 8 and 12 residues loops, respectively, in the challenging modeling scenario in where the side chains of the loop environment are fully remodeled. These results are not only very competitive compared to those obtained with public state of the art methods, but also they are obtained ∼10-fold faster.

PMID:
27151199
PMCID:
PMC4987936
DOI:
10.1093/nar/gkw395
[Indexed for MEDLINE]
Free PMC Article

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