Validation of the alchemical transfer method for the estimation of relative binding affinities of molecular series

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• dc.contributor.author Sabanés Zariquiey, Francesc
• dc.contributor.author Pérez, Adrià
• dc.contributor.author Majewski, Maciej
• dc.contributor.author Gallicchio, Emilio
• dc.contributor.author De Fabritiis, Gianni
• dc.date.accessioned 2024-04-02T15:58:32Z
• dc.date.issued 2023
• dc.description.abstract The accurate prediction of protein-ligand binding affinities is crucial for drug discovery. Alchemical free energy calculations have become a popular tool for this purpose. However, the accuracy and reliability of these methods can vary depending on the methodology. In this study, we evaluate the performance of a relative binding free energy protocol based on the alchemical transfer method (ATM), a novel approach based on a coordinate transformation that swaps the positions of two ligands. The results show that ATM matches the performance of more complex free energy perturbation (FEP) methods in terms of Pearson correlation but with marginally higher mean absolute errors. This study shows that the ATM method is competitive compared to more traditional methods in speed and accuracy and offers the advantage of being applicable with any potential energy function.
• dc.description.sponsorship This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 823712, and the project PID2020-116564GB-I00 has been funded by MCIN/AEI/10.13039/501100011033, the Torres-Quevedo Programme from the Spanish National Agency for Research (PTQ2020-011145/AEI/10.13039/501100011033). Research reported in this publication was supported by the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health under award number GM140090. E.G. acknowledges support from the United States’ National Science Foundation (NSF CAREER 1750511).
• dc.format.mimetype application/pdf
• dc.identifier.citation Sabanés Zariquiey F, Pérez A, Majewski M, Gallicchio E, De Fabritiis G. Validation of the alchemical transfer method for the estimation of relative binding affinities of molecular series. J Chem Inf Model. 2023 Apr 24;63(8):2438-44. DOI: 10.1021/acs.jcim.3c00178
• dc.identifier.doi http://dx.doi.org/10.1021/acs.jcim.3c00178
• dc.identifier.issn 1549-9596
• dc.identifier.uri http://hdl.handle.net/10230/59623
• dc.language.iso eng
• dc.publisher American Chemical Society (ACS)
• dc.relation.ispartof J Chem Inf Model. 2023 Apr 24;63(8):2438-44
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/823712
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-116564GB-I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PTQ2020-011145
• dc.rights This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of chemical information and modeling, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.jcim.3c00178.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Chemical calculations
• dc.subject.keyword Free energy
• dc.subject.keyword Ligands
• dc.subject.keyword Receptors
• dc.subject.keyword Screening assays
• dc.title Validation of the alchemical transfer method for the estimation of relative binding affinities of molecular series
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion