title: Multiscale quantum chemical approaches to QSAR modeling and drug design.
abstract: The comparative use of classical, quantum chemical (QC) ligand-based (LB) and structure-based (SB) quantitative structure-activity relationship (QSAR) results in a detailed and mechanistic-causative description, at different scales (multiscale: classical=macroscopic, LB and SB=electronic-atomistic-nanoscale) and resolution levels, of the energetics and thermodynamics of the binding event for a congeneric set of ligands and/or drugs. QC interaction propensity (reactivity) descriptors in LB QSARs provide an implicitly more accurate estimation of the enthalpic contribution to ligand-target interactions compared with classical QSAR. As for QSAR models from ab initio SB fragment molecular orbital calculations, an explicit enthalpic description of the different additive terms in the computed binding energy is obtainable. Moreover, it is possible to estimate the difference in the free energy change of the ligand-target complex formation and evaluate, on a correlative basis, the contribution of each additive free energy term to the total value.
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, via Campi 183, 41125 Modena, Italy. Electronic address: deben@unimo.it.
authors.forename: Pier G
authors.initials: PG
authors.lastname: De Benedetti
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, via Campi 183, 41125 Modena, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fanelli
mesh_terms: D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship
chemical_list: D008024:Ligands