Alchemical transformations are regularly used to compute free energies of solvation, binding and mutation. The end states of interest are connected by a path using a coupling parameter lambda. The standard procedure is to run multiple simulations, each at a fixed value of lambda, and use Bennett’s acceptance ratio to obtain the free energy difference.
In this webinar we present how the Accelerated Weight histogram method can be used for such calculations. In this approach lambda is varied dynamically in a single simulation, and the free energy difference can be obtained directly. This has been implemented in the GROMACS 2021 release and provides a simple and flexible way to compute alchemical free energies and can be trivially parallelized using multiple walkers (copies of the system).
Berk Hess is a professor of Theoretical Biophysics at KTH. He has designed algorithms for the GROMACS simulation package for over two decades. His current research focuses on advanced sampling methods, aggregation of molecules, and studying wetting of surfaces at the molecular scale.
Magnus has an M.Sc. in Pharmacy from Uppsala University. He finished his Ph.D. in organic chemistry at Stockholm University in 2011, after which he was a postdoc for one year at the Biochemistry department at the University of Cambridge. Since 2012 he has been working in the Molecular Biophysics group in Stockholm, and since 2015 employed by ERCO Pharma to calculate permeability, through the intercellular lipid matrix in the stratum corneum in skin, using MD simulations.
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Title: Applying the Accelerated Weight histogram method to alchemical transformations