Journal article
Toward polarizable AMOEBA thermodynamics at fixed charge efficiency using a dual force field approach: application to organic crystals
Physical chemistry chemical physics : PCCP, Vol.18(44), pp.30313-30322
2016
DOI: 10.1039/C6CP02595A
PMCID: PMC5102770
PMID: 27524378
Abstract
First principles prediction of the structure, thermodynamics and solubility of organic molecular crystals, which play a central role in chemical, material, pharmaceutical and engineering sciences, challenges both potential energy functions and sampling methodologies. Here we calculate absolute crystal deposition thermodynamics using a novel dual force field approach whose goal is to maintain the accuracy of advanced multipole force fields (e.g. the polarizable AMOEBA model) while performing more than 95% of the sampling in an inexpensive fixed charge (FC) force field (e.g. OPLS-AA). Absolute crystal sublimation/deposition phase transition free energies were determined using an alchemical path that grows the crystalline state from a vapor reference state based on sampling with the OPLS-AA force field, followed by dual force field thermodynamic corrections to change between FC and AMOEBA resolutions at both end states (we denote the three step path as AMOEBA/FC). Importantly, whereas the phase transition requires on the order of 200 ns of sampling per compound, only 5 ns of sampling was needed for the dual force field thermodynamic corrections to reach a mean statistical uncertainty of 0.05 kcal mol−1. For five organic compounds, the mean unsigned error between direct use of AMOEBA and the AMOEBA/FC dual force field path was only 0.2 kcal mol−1 and not statistically significant. Compared to experimental deposition thermodynamics, the mean unsigned error for AMOEBA/FC (1.4 kcal mol−1) was more than a factor of two smaller than uncorrected OPLS-AA (3.2 kcal mol−1). Overall, the dual force field thermodynamic corrections reduced condensed phase sampling in the expensive force field by a factor of 40, and may prove useful for protein stability or binding thermodynamics in the future.
Details
- Title: Subtitle
- Toward polarizable AMOEBA thermodynamics at fixed charge efficiency using a dual force field approach: application to organic crystals
- Creators
- Ian J Nessler - Department of Chemical Engineering, University of Iowa, Iowa City, USAJacob M Litman - Department of Biochemistry, University of Iowa, Iowa City, USAMichael J Schnieders - Department of Biochemistry, University of Iowa, Iowa City, USA, Department of Biomedical Engineering
- Resource Type
- Journal article
- Publication Details
- Physical chemistry chemical physics : PCCP, Vol.18(44), pp.30313-30322
- DOI
- 10.1039/C6CP02595A
- PMID
- 27524378
- PMCID
- PMC5102770
- NLM abbreviation
- Phys Chem Chem Phys
- ISSN
- 1463-9076
- eISSN
- 1463-9084
- Grant note
- DOI: 10.13039/100000165, name: Division of Chemistry, award: 1404147; DOI: 10.13039/100000055, name: National Institute on Deafness and Other Communication Disorders, award: R01 DC002842; DOI: 10.13039/100000057, name: National Institute of General Medical Sciences, award: T32 GM008365
- Language
- English
- Date published
- 2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Biochemistry and Molecular Biology
- Record Identifier
- 9984025265802771
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