Combining Machine Learning and Enhanced Sampling Techniques for Efficient and Accurate Calculation of Absolute Binding Free Energies.

ABSTRACT: Calculating absolute binding free energies is challenging and important. In this paper, we test some recently developed metadynamics-based methods and develop a new combination with a Hamiltonian replica-exchange approach. The methods were tested on 18 chemically diverse ligands with a wide range of different binding affinities to a complex target; namely, human soluble epoxide hydrolase. The results suggest that metadynamics with a funnel-shaped restraint can be used to calculate, in a computationally affordable and relatively accurate way, the absolute binding free energy for small fragments. When used in combination with an optimal pathlike variable obtained using machine learning or with the Hamiltonian replica-exchange algorithm SWISH, this method can achieve reasonably accurate resul

SUBMITTER: Evans R 

PROVIDER: S-EPMC7467642 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature