jz1c00189_si_001.pdf (15.86 MB)
DeepBAR: A Fast and Exact Method for Binding Free Energy Computation
journal contribution
posted on 2021-03-05, 22:33 authored by Xinqiang Ding, Bin ZhangThe
fast and accurate calculation of standard binding free energy
has many important applications. Existing methodologies struggle at
balancing accuracy and efficiency. We introduce a new method to compute
binding free energy using deep generative models and the Bennett acceptance
ratio method (DeepBAR). Compared to the rigorous potential of mean
force (PMF) approach that requires sampling from intermediate states,
DeepBAR is an order-of-magnitude more efficient as demonstrated in
a series of host–guest systems. Notably, DeepBAR is exact and
does not suffer from approximations for entropic contributions used
in methods such as the molecular mechanics energy combined with the
generalized Born and surface area continuum solvation (MM/GBSA). We
anticipate DeepBAR to be a valuable tool for computing standard binding
free energy used in drug design.