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Journal of Chemical Theory and Computation
Article . 2018 . Peer-reviewed
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Accelerating QM/MM Free Energy Computations via Intramolecular Force Matching

Authors: Phillip S. Hudson; Stefan Boresch; David M. Rogers; H. Lee Woodcock;

Accelerating QM/MM Free Energy Computations via Intramolecular Force Matching

Abstract

The calculation of free energy differences between levels of theory has numerous potential pitfalls. Chief among them is the lack of overlap, i.e., ensembles generated at one level of theory (e.g., "low") not being good approximations of ensembles at the other (e.g., "high"). Numerous strategies have been devised to mitigate this issue. However, the most straightforward approach is to ensure that the "low" level ensemble more closely resembles that of the "high". Ideally, this is done without increasing computational cost. Herein, we demonstrate that by reparametrizing classical intramolecular potentials to reproduce high level forces (i.e., force matching) configurational overlap between a "low" (i.e., classical) and "high" (i.e., quantum) level can be significantly improved. This procedure is validated on two test cases and results in vastly improved convergence of free energy simulations.

Countries
United States, Austria, United States
Keywords

POTENTIALS, QUANTUM-MECHANICAL CALCULATIONS, NONEQUILIBRIUM WORK METHODS, PERTURBATION CALCULATIONS, 540, 530, FIELDS, 104017 Physikalische Chemie, SIMULATIONS, 102009 Computer simulation, SOLVATION, HYDRATION FREE-ENERGY, BINDING, 104017 Physical chemistry, CHARMM, 102009 Computersimulation

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
47
Top 10%
Top 10%
Top 10%
bronze