title: λ-Meta Dynamics Approach To Compute Absolute Solvation Free Energy.
abstract: We present a new approach to combineλdynamics with meta-dynamics (namedλ-meta dynamics) to compute free energy surface with respect toλ. Particularly, theλ-meta dynamics method extends meta-dynamics to a single virtual variableλ, i.e., the coupling parameter between solute and solvent, to compute absolute solvation free energy as an exemplary application. We demonstrate thatλ-meta dynamics simulations can recover the accurate potential of mean force surface with respect toλcompared to the benchmark results from traditionalλ-dynamics with umbrella sampling. The solvation free energy results for five small organic molecules fromλ-meta dynamics simulations using the same filling scheme show that the statistical errors are within ±0.5 kcal/mol. The newλ-meta dynamics method is general and other variables such as order parameters to describe conformational changes can be easily combined withλ-meta dynamics. This should allow for efficient samplings on high-dimension free energy landscapes.
authors.affiliation: Department of Chemistry, Duke University, 27708.
authors.forename: Pan
authors.initials: P
authors.lastname: Wu
authors.forename: Xiangqian
authors.initials: X
authors.lastname: Hu
authors.forename: Weitao
authors.initials: W
authors.lastname: Yang
keywords: Meta-dynamics; QM/MM; solvation free energy; λ dynamics; λ-meta dynamics