We introduce an effective technique for the calculation of the binding free energy in drug-receptor systems using nonequilibrium molecular dynamics and application of the Jarzynski theorem. In essence, this novel methodology constitutes the nonequilibrium adaptation of an ancient free energy perturbation technique called Double Annihilation Method, invented more than 25 years ago [J. Chem. Phys. 1988, 89, 3742–3746] and upon which modern approaches of binding free energy computation in drug-receptor systems are heavily based. The proposed computational approach, termed Fast Switching Double Annihilation Methods (FS-DAM) in honor of its ancient ancestor, is applied to a prototypical example system with multiple binding sites, proving its computational potential and versatility in unraveling multiple site or allosteric binding processes.

Efficient Nonequilibrium Method for Binding Free Energy Calculations in Molecular Dynamics Simulations / Robert B. Sandberg; Martina Banchelli; Carlo Guardiani; Stefano Menichetti; Gabriella Caminati; Piero Procacci. - In: JOURNAL OF CHEMICAL THEORY AND COMPUTATION. - ISSN 1549-9618. - STAMPA. - 11:(2015), pp. 423-435. [10.1021/ct500964e]

Efficient Nonequilibrium Method for Binding Free Energy Calculations in Molecular Dynamics Simulations

BANCHELLI, MARTINA;GUARDIANI, CARLO;MENICHETTI, STEFANO;CAMINATI, GABRIELLA;PROCACCI, PIERO
2015

Abstract

We introduce an effective technique for the calculation of the binding free energy in drug-receptor systems using nonequilibrium molecular dynamics and application of the Jarzynski theorem. In essence, this novel methodology constitutes the nonequilibrium adaptation of an ancient free energy perturbation technique called Double Annihilation Method, invented more than 25 years ago [J. Chem. Phys. 1988, 89, 3742–3746] and upon which modern approaches of binding free energy computation in drug-receptor systems are heavily based. The proposed computational approach, termed Fast Switching Double Annihilation Methods (FS-DAM) in honor of its ancient ancestor, is applied to a prototypical example system with multiple binding sites, proving its computational potential and versatility in unraveling multiple site or allosteric binding processes.
2015
11
423
435
Robert B. Sandberg; Martina Banchelli; Carlo Guardiani; Stefano Menichetti; Gabriella Caminati; Piero Procacci
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/966587
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