Using parallelized incremental meta-docking can solve the conformational sampling issue when docking large ligands to proteins

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dc.citation.articleNumber42en_US
dc.citation.journalTitleBMC Molecular and Cell Biologyen_US
dc.citation.volumeNumber20en_US
dc.contributor.authorDevaurs, Didieren_US
dc.contributor.authorAntunes, Dinler A.en_US
dc.contributor.authorHall-Swan, Sarahen_US
dc.contributor.authorMitchell, Nicoleen_US
dc.contributor.authorMoll, Marken_US
dc.contributor.authorLizée, Gregoryen_US
dc.contributor.authorKavraki, Lydia E.en_US
dc.date.accessioned2019-11-14T17:52:27Zen_US
dc.date.available2019-11-14T17:52:27Zen_US
dc.date.issued2019en_US
dc.description.abstractBackground: Docking large ligands, and especially peptides, to protein receptors is still considered a challenge in computational structural biology. Besides the issue of accurately scoring the binding modes of a protein-ligand complex produced by a molecular docking tool, the conformational sampling of a large ligand is also often considered a challenge because of its underlying combinatorial complexity. In this study, we evaluate the impact of using parallelized and incremental paradigms on the accuracy and performance of conformational sampling when docking large ligands. We use five datasets of protein-ligand complexes involving ligands that could not be accurately docked by classical protein-ligand docking tools in previous similar studies. Results: Our computational evaluation shows that simply increasing the amount of conformational sampling performed by a protein-ligand docking tool, such as Vina, by running it for longer is rarely beneficial. Instead, it is more efficient and advantageous to run several short instances of this docking tool in parallel and group their results together, in a straightforward parallelized docking protocol. Even greater accuracy and efficiency are achieved by our parallelized incremental meta-docking tool, DINC, showing the additional benefits of its incremental paradigm. Using DINC, we could accurately reproduce the vast majority of the protein-ligand complexes we considered. Conclusions: Our study suggests that, even when trying to dock large ligands to proteins, the conformational sampling of the ligand should no longer be considered an issue, as simple docking protocols using existing tools can solve it. Therefore, scoring should currently be regarded as the biggest unmet challenge in molecular docking.en_US
dc.identifier.citationDevaurs, Didier, Antunes, Dinler A., Hall-Swan, Sarah, et al.. "Using parallelized incremental meta-docking can solve the conformational sampling issue when docking large ligands to proteins." <i>BMC Molecular and Cell Biology,</i> 20, (2019) Biomed Central: https://doi.org/10.1186/s12860-019-0218-z.en_US
dc.identifier.digitals12860-019-0218-zen_US
dc.identifier.doihttps://doi.org/10.1186/s12860-019-0218-zen_US
dc.identifier.urihttps://hdl.handle.net/1911/107687en_US
dc.language.isoengen_US
dc.publisherBiomed Centralen_US
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/),en_US
dc.titleUsing parallelized incremental meta-docking can solve the conformational sampling issue when docking large ligands to proteinsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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