Papers › Alchemical Transformations for Single-Step Hydration Free Energy Calculations

Alchemical Transformations for Single-Step Hydration Free Energy Calculations

13 May 2020arXiv:2005.06504archive 2025-07-28

Emilio Gallicchio

We present a family of alchemical perturbation potentials that allow the calculation of hydration free energy of small to medium-sized molecules in a single perturbation step. We also present a general framework to optimize the parameters of the alchemical perturbation potentials based on avoiding first order pseudo phase transitions along the alchemical path. We illustrate the method for two compounds of increasing size and complexity: ethanol and 1-naphtol. In each case we show that convergence of the hydration free energy is achieved rapidly when conventional approaches fail.

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