Sabanés Zariquiey, FrancescPérez, AdriàMajewski, MaciejGallicchio, EmilioDe Fabritiis, Gianni2024-04-022023Sabanés 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.3c001781549-9596http://hdl.handle.net/10230/59623The 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.application/pdfengThis 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.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1021/acs.jcim.3c00178Chemical calculationsFree energyLigandsReceptorsScreening assaysinfo:eu-repo/semantics/openAccess