Moreno, DavidZivanovic, SanjaColizzi, FrancescoHospital Gasch, AdamAranda, JuanSoliva, RobertOrozco López, Modesto2021-07-192021-08-282020-08-281549-9626https://hdl.handle.net/2445/179168We present drug force-field recalibration (DFFR), a new method for refining of automatic force-fields used to represent small drugs in docking and molecular dynamics simulations. The method is based on fine-tuning of torsional terms to obtain ensembles that reproduce observables derived from reference data. DFFR is fast and flexible and can be easily automatized for a high-throughput regime, making it useful in drug-design projects. We tested the performance of the method in a few model systems and also in a variety of druglike molecules using reference data derived from: (i) density functional theory coupled to a self-consistent reaction field (DFT/SCRF) calculations on highly populated conformers and (ii) enhanced sampling quantum mechanical/molecular mechanics (QM/MM) where the drug is reproduced at the QM level, while the solvent is represented by classical force-fields. Extension of the method to include other sources of reference data is discussed.10 p.application/pdfeng(c) American Chemical Society, 2020Disseny de medicamentsDinàmica molecularMolecular dynamicsDrug designinfo:eu-repo/semantics/article2021-07-15info:eu-repo/semantics/openAccess6467279