Accelerating Convergence of Free Energy Computations with Hamiltonian Simulated Annealing of Solvent (HSAS)
Journal Article
·
· Journal of Chemical Theory and Computation
- Argonne National Lab. (ANL), Argonne, IL (United States). Computational Science Division
Coupling between binding of a ligand to a receptor and the displacement of a number of bound water molecules is a common event in molecular recognition processes. When the binding site is deeply buried and the exchange of water molecules with the bulk region is difficult to sample, the convergence and accuracy in free energy calculations can be severely compromised. Traditionally, Grand Canonical Monte Carlo (GCMC) based methods have been used to accelerate equilibration of water-at the expense, however, of lengthy trials before a molecular dynamics (MD) simulation. In this paper, a user-friendly and cost-efficient method, Hamiltonian simulated annealing of solvent in combination with lambda-exchange of free energy perturbation (FEP) is proposed to accelerate the sampling of water molecules in free energy calculations. As an illustrative example with reliable data from previous GCMC simulations, absolute binding affinity of camphor to cytochrome P450 was calculated. The simulated hydration state change in the buried binding pocket quantitatively agrees with GCMC simulations. Finally, it is shown that the new protocol significantly accelerates sampling of water in a buried binding pocket and the convergence of free energy, with negligible setup and computing costs compared to GCMC methods.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States); USDOE Office of Science (SC), Advanced Scientific Computing Research (ASCR) (SC-21)
- Grant/Contract Number:
- AC02-06CH11357
- OSTI ID:
- 1510273
- Journal Information:
- Journal of Chemical Theory and Computation, Journal Name: Journal of Chemical Theory and Computation Journal Issue: 4 Vol. 15; ISSN 1549-9618
- Publisher:
- American Chemical SocietyCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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