title: Alchemical determination of drug-receptor binding free energy: Where we stand and where we could move to.
abstract: Alchemical molecular dynamics simulations for evaluating the binding free energy in ligand-receptor systems are emerging a new powerful tool for in silico drug discovery projects. Nonetheless, theoretical and technical challenges for these methodologies remain high and their use in industrial applications is still limited. In this contribution, the many variants of the alchemical approach are critically revised, discussing their strengths as well as their pitfalls and entanglements and placing existing computational theories into the broader context of nonequilibrium thermodynamics.
authors.affiliation: Department of Chemistry, University of Florence, Italy. Electronic address: procacci@unifi.it.
authors.forename: Piero
authors.initials: P
authors.lastname: Procacci
mesh_terms: D055808:Drug Discovery; D019277:Entropy; D006801:Humans; D008024:Ligands; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011955:Receptors, Drug / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011955:Receptors, Drug
keywords: Alchemical simulations; Binding free energy; Crooks theorem; Drug-receptor; Hamiltonian Replica Exchange; Jarzynski theorem; Molecular dynamics; Nonequilibrium process; Solute tempering