Replica-Exchange Enveloping Distribution Sampling: Calculation of Relative Free Energies in GROMOS

Authors

DOI:

https://doi.org/10.2533/chimia.2022.327

Keywords:

Computational Chemistry, Free Energy, RE-EDS

Abstract

Molecular dynamics (MD) simulations have become an important tool to investigate biological systems. Free-energy calculations based on MD are playing an increasingly important role for computer-aided drug design and material discovery in recent years. Free-energy differences between pairs of end-states can be estimated using well-established methods such as thermodynamic integration (TI) or Bennett’s acceptance ratio (BAR). An attractive alternative is the recently developed replica-exchange enveloping distribution sampling (RE-EDS) method, which enables estimating relative free-energy differences between multiple molecules from a single simulation. Here, we provide an introduction to the principles underlying RE-EDS and give an overview of the RE-EDS pipeline. In addition, we provide a description of the two complementary tools RestraintMaker and amber2gromos. We briefly discuss the findings of three recent applications of RE-EDS to calculate relative binding or hydration free energies. In all three studies, good agreement was found between the results obtained using RE-EDS and experimental values as well as
values obtained using other free-energy methods.

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Published

2022-04-27

How to Cite

[1]
S. R. Rieder, B. Ries, C. Champion, E. P. Barros, P. H. Hünenberger, S. Riniker, Chimia 2022, 76, 327, DOI: 10.2533/chimia.2022.327.