Using Multistate Reweighting to Rapidly and Efficiently Explore Molecular Simulation Parameters Space for Nonbonded Interactions

Paliwal, Himanshu; Shirts, Michael R.

doi:10.1021/ct4005068

Cited by 19 publications

(27 citation statements)

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“…A switched cut-off between 1.0 and 1.1 nm was used for dispersion interactions and long-range dispersion corrections were applied to both energy and pressure. Use of these long-range corrections ensures that the free energy results are independent of cutoff radius, provided it is at least 0.9 nm [17,32]. As explained previously, the starting point for the improved model is the TraPPE force-field.…”

Section: -Computational Methodsmentioning

confidence: 99%

Predicting hydrophobic solvation by molecular simulation: 2. New united‐atom model for alkanes, alkenes, and alkynes

Jorge

2016

J Comput Chem

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This version is available at https://strathprints.strath.ac.uk/59034/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Strathprints administrator: strathprints@strath.ac.ukThe Strathprints institutional repository (https://strathprints.strath.ac.uk) is a digital archive of University of Strathclyde research outputs. It has been developed to disseminate open access research outputs, expose data about those outputs, and enable the management and persistent access to Strathclyde's intellectual output. Predicting Hydrophobic Solvation by Molecular Simulation: 2. New United-atom Model for Alkanes, Alkenes and AlkynesMiguel Jorge* Department of Chemical and Process Engineering, University of Strathclyde, 75 MontroseStreet, Glasgow G1 1XJ, United Kingdom Email -miguel.jorge@strath.ac.uk Abstract: Existing united-atom models for non-polar hydrocarbons lead to systematic deviations in predicted solvation free energies in hydrophobic solvents. In this paper, an improved set of parameters is proposed for alkane molecules that corrects this systematic deviation and accurately predicts solvation free energies in hydrophobic media, while simultaneously providing a very good description of pure liquid densities. The model is then extended to alkenes and alkynes, again yielding very accurate predictions of solvation free energies and densities for these classes of compounds. For alkynes in particular, this work represents the first attempt at a systematic parameterization using the united-atom approach. Averaging over all 95 solute/solvent pairs tested, the mean signed deviation from experimental data is very close to zero, indicating no systematic error in the predictions. The fact that predictions are robust even for relatively large molecules suggests that the new model may be applicable to solvation of non-polar macromolecules without accumulation of errors. The root mean squared deviation of the simulations is only 0.6 kJ/mol, which is lower than the estimated uncertainty in the experimental measurements. This excellent performance constitutes a solid basis upon which a more general model can be parameterized to describe solvation in both polar and non-polar environments.Keywords: Solubility; Molecular Simulation; hydrocarbons; non-polar; free energy -IntroductionPredicting solvation in hydrophobic environments is r...

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Section: -Computational Methodsmentioning

confidence: 99%

Predicting hydrophobic solvation by molecular simulation: 2. New united‐atom model for alkanes, alkenes, and alkynes

Jorge

2016

J Comput Chem

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“…6,21,22 The close relation between EMUS and MBAR indicates that error analysis of EMUS may provide insight into the sources of error in MBAR for these problems, but we do not pursue this idea further in the present work.…”

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confidence: 99%

Eigenvector method for umbrella sampling enables error analysis

Thiede

Koten

Weare

et al. 2016

The Journal of Chemical Physics

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Umbrella sampling efficiently yields equilibrium averages that depend on exploring rare states of a model by biasing simulations to windows of coordinate values and then combining the resulting data with physical weighting. Here, we introduce a mathematical framework that casts the step of combining the data as an eigenproblem. The advantage to this approach is that it facilitates error analysis. We discuss how the error scales with the number of windows. Then, we derive a central limit theorem for averages that are obtained from umbrella sampling. The central limit theorem suggests an estimator of the error contributions from individual windows, and we develop a simple and computationally inexpensive procedure for implementing it. We demonstrate this estimator for simulations of the alanine dipeptide and show that it emphasizes low free energy pathways between stable states in comparison to existing approaches for assessing error contributions. Our work suggests the possibility of using the estimator and, more generally, the eigenvector method for umbrella sampling to guide adaptation of the simulation parameters to accelerate convergence. Published by AIP Publishing. [http://dx

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“…, calculated with MBAR, which can take into account statistical correlations between the expectation of ∆U (T ) and the log partition function ∆G(T ) take into account [210].…”

Section: ∆U (T )−∆G(t ) Tmentioning

confidence: 99%

Capturing the Role of Temperature and Entropy in Crystal Polymorphs Through Molecular Simulations

Dybeck

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AcknowledgementsI would like to acknowledge the guidance and support provided by my advisor MichaelShirts. I would also like to thank Levi Naden, Natalie Schieber, Nate Abraham and the entire Shirts group for their help and technical support during my research. I also would like to acknowledge the UVA high performance computing team for the computational resources necessary to complete this work. Finally, I would like to acknowledge the endless love and support that my friends and family provided me during this challenging Ph.D. journey.iii AbstractThe presence of multiple stable crystal structures in solid organic materials can limit their commercial viability when two or more observable polymorphs exhibit markedly different physical properties. Unintended restructuring events have hindered pharmaceutical solid form development in numerous therapeutic candidates and have led to costly market recalls.Conversely, intentional synthesis of a metastable form has led to significantly more favorable performance in numerous materials.Current computational methods for predicting polymorphic behavior evaluate candidate crystal structures based on the minimized lattice energy. However, these static lattice energybased approaches generate far more lattice energy minima than there are experimentally observed structures. Thermal motion of the crystals under working conditions has the potential to explain why many of these lattice minima are not observed experimentally. Lattice minima that are identified from a static crystal structure prediction can ultimately be unstable at experimental conditions through either temperature-mediated stability reranking, kinetic interconversion of multiple minima, or inaccuracies of the energy function in producing the real crystal ensemble.In this work, we explore the role of thermal motion in eliminating candidate crystal structures using fully atomistic molecular dynamics simulations. Enthalpically favorable structures with low entropy will become unfavorable at high temperatures through temperaturemediated stability reranking. Our simulations correctly identify the high temperature solid form as having a larger entropy than the low temperature form in twelve small molecule organic systems with known temperature-mediated transformations. The estimated entropy differences in the classical point-charge potential are significantly closer to experimental measurements than estimated enthalpy differences. This result suggests that entropy difference estimates are less sensitive to the complexity of the simulation potential than the corresponding enthalpy estimates. We additionally find that a cheaper harmonic approximation provides a sufficient estimate of entropic contributions in small rigid molecules. However, entropies with iv the harmonic approximation diverge from molecular dynamics-derived entropies in systems with multiple rotatable degrees of freedom or dynamically disordered crystalline structures.We additionally probe the sensitivity of the stability estimates to the energy function ...

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Using Multistate Reweighting to Rapidly and Efficiently Explore Molecular Simulation Parameters Space for Nonbonded Interactions

Cited by 19 publications

References 55 publications

Predicting hydrophobic solvation by molecular simulation: 2. New united‐atom model for alkanes, alkenes, and alkynes

Predicting hydrophobic solvation by molecular simulation: 2. New united‐atom model for alkanes, alkenes, and alkynes

Eigenvector method for umbrella sampling enables error analysis

Capturing the Role of Temperature and Entropy in Crystal Polymorphs Through Molecular Simulations

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