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Generalized alteration of structure and parameters: A new method for free‐energy perturbations in systems containing flexible degrees of freedom
Author(s) -
Severance Daniel L.,
Essex Jonathan W.,
Jorgensen William L.
Publication year - 1995
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.540160306
Subject(s) - degrees of freedom (physics and chemistry) , free energy perturbation , perturbation (astronomy) , energy (signal processing) , computer science , mathematics , physics , computational chemistry , molecular dynamics , chemistry , thermodynamics , statistics , quantum mechanics
Abstract A modified derivation of the free energy perturbation (FEP) equation leads to a more general interpretation of the procedures for generating the geometry of a perturbed molecule from the reference one in FEP simulations of flexible systems. Using this form of the equation, it is possible to implement a wide variety of procedures which heretofore would have been considered impossible. A new method, generalized alteration of structure and parameters (GASP), has been implemented in the BOSS program and has been found to be more efficient for perturbations of harmonic degrees of freedom than the commonly adopted procedure. Additionally, an extreme example for which the new procedure proves less satisfactory is presented, and a more efficient method which is also derived from the new form of the FEP equation is devised and tested. It is concluded that the key to a convergent FEP method is efficient sampling of low‐energy configurations of the perturbed state; the new form of the equation suggests ways of generating such configurations. © 1995 by John Wiley & Sons, Inc.