Association of unconstrained molecular dynamics (MD) and the formalisms of thermodynamic integration and average force [Darve and Pohorille, J. Chem. Phys. 115, 9169 (2001)] have been employed to determine potentials of mean force. When implemented in a general MD code, the additional computational effort, compared to other standard, unconstrained simulations, is marginal. The force acting along a chosen reaction coordinate ξ is estimated from the individual forces exerted on the chemical system and accumulated as the simulation progresses. The estimated free energy derivative computed for small intervals of ξ is canceled by an adaptive bias to overcome the barriers of the free energy landscape. Evolution of the system along the reaction coordinate is, thus, limited by its sole self-diffusion properties. The illustrative examples of the reversible unfolding of deca-L-alanine, the association of acetate and guanidinium ions in water, the dimerization of methane in water, and its transfer across the water liquid-vapor interface are examined to probe the efficiency of the method.
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Research Article| July 30 2004
Overcoming free energy barriers using unconstrained molecular dynamics simulations
Jérôme Hénin, Christophe Chipot; Overcoming free energy barriers using unconstrained molecular dynamics simulations. J. Chem. Phys. 15 August 2004; 121 (7): 2904–2914. https://doi.org/10.1063/1.1773132
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