Replica-Exchange Enveloping Distribution Sampling Using Generalized AMBER Force-Field Topologies: Application to Relative Hydration Free-Energy Calculations for Large Sets of Molecules
Salomé R. Rieder, Benjamin Ries, Kay Schaller, Candide Champion, Emília P. Barros, Philippe H. Hünenberger, Sereina Riniker
Abstract
, to compute relative hydration free energies for a series of benzene derivatives. The results obtained with RE-EDS are compared to the experimental data as well as calculated values from the literature. In addition, the estimated free-energy differences in water and in vacuum are compared to values from TI calculations carried out with GROMACS. The hydration free energies obtained using RE-EDS for multiple molecules are found to be in good agreement with both the experimental data and the results calculated using other free-energy methods. While all considered free-energy methods delivered accurate results, the RE-EDS calculations required the least amount of total simulation time. This work serves as a validation for the use of GAFF topologies with the GROMOS simulation package and the RE-EDS approach. Furthermore, the performance of RE-EDS for a large set of 28 end-states is assessed with promising results.