choderalab/openmmtools: 0.19.0 - Multiple alchemical regions

Rizzi, Andrea; Chodera, John D.; Naden, Levi N.; Beauchamp, Kyle A.; Grinaway, Patrick; Fass, Josh; adw,; Rustenburg, Bas; Ross, Gregory A.; Krämer, Andreas; Macdonald, Hannah E. Bruce; Swenson, David W.; Simmonett, Andy; hb,; ajsilveira,

doi:10.5281/zenodo.3532826

Cited by 2 publications

(1 citation statement)

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“…8 C . This approach is also referred to as self adjusted mixture sampling [140,141,172] and while promising, has so far only been supported in OpenMM Tools [173]. The last approach makes use of non-equilibrium simulations [7].…”

Section: Which Sampling Scheme Will Work Best For My Problem?mentioning

confidence: 99%

Best Practices for Alchemical Free Energy Calculations

Mey,

Allen,

Macdonald

et al. 2020

Preprint

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Alchemical free energy calculations are a useful tool for predicting free energy differences associated with the transfer of molecules from one environment to another. The hallmark of these methods is the use of "bridging" potential energy functions representing alchemical intermediate states that cannot exist as real chemical species. The data collected from these bridging alchemical thermodynamic states allows the efficient computation of transfer free energies (or differences in transfer free energies) with orders of magnitude less simulation time than simulating the transfer process directly. While these methods are highly flexible, care must be taken in avoiding common pitfalls to ensure that computed free energy differences can be robust and reproducible for the chosen force field, and that appropriate corrections are included to permit direct comparison with experimental data. In this paper, we review current best practices for several popular application domains of alchemical free energy calculations, including relative and absolute small molecule binding free energy calculations to biomolecular targets.

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Section: Which Sampling Scheme Will Work Best For My Problem?mentioning

confidence: 99%

Best Practices for Alchemical Free Energy Calculations

Mey,

Allen,

Macdonald

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Membrane permeability of small molecules from unbiased molecular dynamics simulations

Krämer

Ghysels

Wang

et al. 2020

The Journal of Chemical Physics

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Permeation of many small molecules through lipid bilayers can be directly observed in molecular dynamics simulations on the nano-and microsecond timescale. While unbiased simulations provide an unobstructed view of the permeation process, their feasibility for computing permeability coefficients depends on various factors that differ for each permeant. The present work studies three small molecules for which unbiased simulations of permeation are feasible within less than a microsecond, one hydrophobic (oxygen), one hydrophilic (water), and one amphiphilic (ethanol). Permeabilities are computed using two approaches: counting methods and a maximumlikelihood estimation for the inhomogeneous solubility diffusion (ISD) model. Counting methods yield nearly model-free estimates of the permeability for all three permeants. While the ISD-based approach is reasonable for oxygen, it lacks precision for water due to insufficient sampling, and results in misleading estimates for ethanol due to invalid model assumptions. It is also demonstrated that simulations using a Langevin thermostat with collision frequencies of 1/ps and 5/ps yield oxygen permeabilities and diffusion constants that are lower than those using Nose-Hoover by statistically significant margins. In contrast, permeabilities from trajectories generated with Nosé-Hoover and the microcanonical ensemble do not show statistically significant differences. As molecular simulations become more affordable and accurate, calculation of permeability for an expanding range of molecules will be feasible using unbiased simulations. The present work summarizes theoretical underpinnings, identifies pitfalls and develops best practices for such simulations.

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choderalab/openmmtools: 0.19.0 - Multiple alchemical regions

Cited by 2 publications

References 0 publications

Best Practices for Alchemical Free Energy Calculations

Best Practices for Alchemical Free Energy Calculations

Membrane permeability of small molecules from unbiased molecular dynamics simulations

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