We present a parameterized analytical model of alchemical molecular binding. The model describes accurately the free energy profiles of alchemical transformations obtained from molecular dynamics simulations. The parameters of the model, which are physically motivated, are obtained by maximum-likelihood fitting of model predictions to numerical simulations. The validity of the model has been assessed on a set of host-guest and protein-ligand complexes. The model faithfully reproduces both the binding free energy profiles and the probability densities of the perturbation energy as a function of the alchemical progress parameter lambda. The model offers a rationalization for the characteristic shape of the free energy profiles. The parameters obtained from the model are novel useful descriptors of protein-ligand systems and can be used to aid the discovery and classification of potential binders.

Alchemical response parameters from an analytical model of molecular binding

256th National Meeting (2018)

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