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RCD+: Fast loop modeling server
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 (...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987936/ https://www.ncbi.nlm.nih.gov/pubmed/27151199 http://dx.doi.org/10.1093/nar/gkw395 |
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author | López-Blanco, José Ramón Canosa-Valls, Alejandro Jesús Li, Yaohang Chacón, Pablo |
author_facet | López-Blanco, José Ramón Canosa-Valls, Alejandro Jesús Li, Yaohang Chacón, Pablo |
author_sort | López-Blanco, José Ramón |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4987936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-49879362016-08-22 RCD+: Fast loop modeling server López-Blanco, José Ramón Canosa-Valls, Alejandro Jesús Li, Yaohang Chacón, Pablo Nucleic Acids Res Web Server issue 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. Oxford University Press 2016-07-08 2016-05-05 /pmc/articles/PMC4987936/ /pubmed/27151199 http://dx.doi.org/10.1093/nar/gkw395 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Web Server issue López-Blanco, José Ramón Canosa-Valls, Alejandro Jesús Li, Yaohang Chacón, Pablo RCD+: Fast loop modeling server |
title | RCD+: Fast loop modeling server |
title_full | RCD+: Fast loop modeling server |
title_fullStr | RCD+: Fast loop modeling server |
title_full_unstemmed | RCD+: Fast loop modeling server |
title_short | RCD+: Fast loop modeling server |
title_sort | rcd+: fast loop modeling server |
topic | Web Server issue |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987936/ https://www.ncbi.nlm.nih.gov/pubmed/27151199 http://dx.doi.org/10.1093/nar/gkw395 |
work_keys_str_mv | AT lopezblancojoseramon rcdfastloopmodelingserver AT canosavallsalejandrojesus rcdfastloopmodelingserver AT liyaohang rcdfastloopmodelingserver AT chaconpablo rcdfastloopmodelingserver |