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.

Multiscale quantum chemical approaches to QSAR modeling and drug design / DE BENEDETTI, Pier Giuseppe; Fanelli, Francesca. - In: DRUG DISCOVERY TODAY. - ISSN 1359-6446. - ELETTRONICO. - 19:12(2014), pp. 1921-1927. [10.1016/j.drudis.2014.09.024]

Multiscale quantum chemical approaches to QSAR modeling and drug design

DE BENEDETTI, Pier Giuseppe;FANELLI, Francesca
2014

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.
2014
19
12
1921
1927
Multiscale quantum chemical approaches to QSAR modeling and drug design / DE BENEDETTI, Pier Giuseppe; Fanelli, Francesca. - In: DRUG DISCOVERY TODAY. - ISSN 1359-6446. - ELETTRONICO. - 19:12(2014), pp. 1921-1927. [10.1016/j.drudis.2014.09.024]
DE BENEDETTI, Pier Giuseppe; Fanelli, Francesca
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1060887
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