Improvement in the Predicted Partitioning of Alcohol and Polyethylene Oxide Groups Between Water and Octanol (logP) in Molecular Dynamics Simulations

Dallas B. Warren, Emma McPhee, Woldeamanuel A. Birru, Hassan Benameur, David K. Chalmers, Colin W. Pouton

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Molecular dynamics simulations can be applied to explore the complex liquid phase behavior of lipid-based formulations and the gastrointestinal tract lumen. In order for the results from these simulations to be of value, the manner in which molecules interact with both aqueous and oil phases present needs to be as correct as possible. An existing molecular dynamics force field, GROMOS 53a6, was demonstrated to poorly reproduce the partitioning of straight-chain alcohol and short-chain polyethylene glycol (PEG) molecules between octanol and water phase (logP), with the molecules too hydrophobic. Force field parameters for Lennard-Jones interactions between CH2 and CH3 with water oxygen were adjusted to reproduce the experimental octanol logP, with all other Lennard-Jones and force field parameters left untouched. This parameter set, called 53a6 DBW , was subsequently used to recalculate straight-chain alcohol and short-chain PEG molecules, with significant improvement in the values obtained. Simulations of a nonionic surfactant in water, octaethylene glycol monocaprylate, were also performed to observe the aggregation behavior. 53a6 DBW demonstrated significant improvements in water interactions with the PEG chains, well hydrating the PEG groups, and allowing the formation of micelles. Further improvements and evaluation of the improved parameter set are ongoing.

Original languageEnglish
Pages (from-to)214-222
Number of pages9
JournalJournal of Pharmaceutical Sciences
Volume108
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • drug delivery system(s)
  • excipient(s)
  • force field
  • in silico modeling
  • molecular dynamics
  • solubilization
  • surfactant(s)

Cite this

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title = "Improvement in the Predicted Partitioning of Alcohol and Polyethylene Oxide Groups Between Water and Octanol (logP) in Molecular Dynamics Simulations",
abstract = "Molecular dynamics simulations can be applied to explore the complex liquid phase behavior of lipid-based formulations and the gastrointestinal tract lumen. In order for the results from these simulations to be of value, the manner in which molecules interact with both aqueous and oil phases present needs to be as correct as possible. An existing molecular dynamics force field, GROMOS 53a6, was demonstrated to poorly reproduce the partitioning of straight-chain alcohol and short-chain polyethylene glycol (PEG) molecules between octanol and water phase (logP), with the molecules too hydrophobic. Force field parameters for Lennard-Jones interactions between CH2 and CH3 with water oxygen were adjusted to reproduce the experimental octanol logP, with all other Lennard-Jones and force field parameters left untouched. This parameter set, called 53a6 DBW , was subsequently used to recalculate straight-chain alcohol and short-chain PEG molecules, with significant improvement in the values obtained. Simulations of a nonionic surfactant in water, octaethylene glycol monocaprylate, were also performed to observe the aggregation behavior. 53a6 DBW demonstrated significant improvements in water interactions with the PEG chains, well hydrating the PEG groups, and allowing the formation of micelles. Further improvements and evaluation of the improved parameter set are ongoing.",
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author = "Warren, {Dallas B.} and Emma McPhee and Birru, {Woldeamanuel A.} and Hassan Benameur and Chalmers, {David K.} and Pouton, {Colin W.}",
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Improvement in the Predicted Partitioning of Alcohol and Polyethylene Oxide Groups Between Water and Octanol (logP) in Molecular Dynamics Simulations. / Warren, Dallas B.; McPhee, Emma; Birru, Woldeamanuel A.; Benameur, Hassan; Chalmers, David K.; Pouton, Colin W.

In: Journal of Pharmaceutical Sciences, Vol. 108, No. 1, 01.01.2019, p. 214-222.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Benameur, Hassan

AU - Chalmers, David K.

AU - Pouton, Colin W.

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