Overcoming dissipation in the calculation of standard binding free energies by ligand extraction.

ABSTRACT: This article addresses calculations of the standard free energy of binding from molecular simulations in which a bound ligand is extracted from its binding site by steered molecular dynamics (MD) simulations or equilibrium umbrella sampling (US). Host-guest systems are used as test beds to examine the requirements for obtaining the reversible work of ligand extraction. We find that, for both steered MD and US, marked irreversibilities can occur when the guest molecule crosses an energy barrier and suddenly jumps to a new position, causing dissipation of energy stored in the stretched molecule(s). For flexible molecules, this occurs even when a stiff pulling spring is used, and it is difficult to suppress in calculations where the spring is attached to the molecules by single, fixed attachm

SUBMITTER: Velez-Vega C 

PROVIDER: S-EPMC3932244 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature