TY - JOUR AU - Rieder, Salomé R. AU - Ries, Benjamin AU - Champion, Candide AU - Barros, Emilia P. AU - Hünenberger, Philippe H. AU - Riniker, Sereina PY - 2022/04/27 Y2 - 2024/03/29 TI - Replica-Exchange Enveloping Distribution Sampling: Calculation of Relative Free Energies in GROMOS JF - CHIMIA JA - Chimia VL - 76 IS - 4 SE - Scientific Articles DO - 10.2533/chimia.2022.327 UR - https://www.chimia.ch/chimia/article/view/2022_327 SP - 327-330 AB - <p>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.</p> ER -