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dc.contributor.authorHall-Swan, Sarah
Devaurs, Didier
Rigo, Mauricio M.
Antunes, Dinler A.
Kavraki, Lydia E.
Zanatta, Geancarlo
dc.date.accessioned 2021-11-11T19:30:20Z
dc.date.available 2021-11-11T19:30:20Z
dc.date.issued 2021
dc.identifier.citation Hall-Swan, Sarah, Devaurs, Didier, Rigo, Mauricio M., et al.. "DINC-COVID: A webserver for ensemble docking with flexible SARS-CoV-2 proteins." Computers in Biology and Medicine, 139, (2021) Elsevier: https://doi.org/10.1016/j.compbiomed.2021.104943.
dc.identifier.urihttps://hdl.handle.net/1911/111646
dc.description.abstract An unprecedented research effort has been undertaken in response to the ongoing COVID-19 pandemic. This has included the determination of hundreds of crystallographic structures of SARS-CoV-2 proteins, and numerous virtual screening projects searching large compound libraries for potential drug inhibitors. Unfortunately, these initiatives have had very limited success in producing effective inhibitors against SARS-CoV-2 proteins. A reason might be an often overlooked factor in these computational efforts: receptor flexibility. To address this issue we have implemented a computational tool for ensemble docking with SARS-CoV-2 proteins. We have extracted representative ensembles of protein conformations from the Protein Data Bank and from in silico molecular dynamics simulations. Twelve pre-computed ensembles of SARS-CoV-2 protein conformations have now been made available for ensemble docking via a user-friendly webserver called DINC-COVID (dinc-covid.kavrakilab.org). We have validated DINC-COVID using data on tested inhibitors of two SARS-CoV-2 proteins, obtaining good correlations between docking-derived binding energies and experimentally-determined binding affinities. Some of the best results have been obtained on a dataset of large ligands resolved via room temperature crystallography, and therefore capturing alternative receptor conformations. In addition, we have shown that the ensembles available in DINC-COVID capture different ranges of receptor flexibility, and that this diversity is useful in finding alternative binding modes of ligands. Overall, our work highlights the importance of accounting for receptor flexibility in docking studies, and provides a platform for the identification of new inhibitors against SARS-CoV-2 proteins.
dc.language.iso eng
dc.publisher Elsevier
dc.rightsThis is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/).
dc.title DINC-COVID: A webserver for ensemble docking with flexible SARS-CoV-2 proteins
dc.type Journal article
dc.citation.journalTitle Computers in Biology and Medicine
dc.citation.volumeNumber 139
dc.identifier.digital 1-s2-0-S001048252100737X-main
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.1016/j.compbiomed.2021.104943
dc.type.publication publisher version
dc.citation.articleNumber 104943


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