Dataset Information

Reparameterization of Solute-Solute Interactions for Amino Acid-Sugar Systems Using Isopiestic Osmotic Pressure Molecular Dynamics Simulations.

ABSTRACT: AMBER/GLYCAM and CHARMM are popular force fields for simulations of amino acids and sugars. Here we report excessively attractive amino acid-sugar interactions in both force fields, and corrections to nonbonded interactions that match experimental osmotic pressures of mixed aqueous solutions of diglycine and sucrose. The modified parameters also improve the ?Gtrans of diglycine from water to aqueous sucrose and, with AMBERff99SB/GLYCAM06, eliminate a caging effect seen in previous simulations of the protein ubiquitin with glucose.

SUBMITTER: Lay WK

PROVIDER: S-EPMC5844349 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Reparameterization of Solute-Solute Interactions for Amino Acid-Sugar Systems Using Isopiestic Osmotic Pressure Molecular Dynamics Simulations.

Lay Wesley K WK Miller Mark S MS Elcock Adrian H AH

Journal of chemical theory and computation 20170428 5

AMBER/GLYCAM and CHARMM are popular force fields for simulations of amino acids and sugars. Here we report excessively attractive amino acid-sugar interactions in both force fields, and corrections to nonbonded interactions that match experimental osmotic pressures of mixed aqueous solutions of diglycine and sucrose. The modified parameters also improve the ΔG<sub>trans</sub> of diglycine from water to aqueous sucrose and, with AMBERff99SB/GLYCAM06, eliminate a caging effect seen in previous sim ...[more]

PMID: 28437100

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Project description:There is a small, but growing, body of literature describing the use of osmotic coefficient measurements to validate and reparametrize simulation force fields. Here we have investigated the ability of five very commonly used force field and water model combinations to reproduce the osmotic coefficients of seven neutral amino acids and five small molecules. The force fields tested include AMBER ff99SB-ILDN, CHARMM36, GROMOS54a7, and OPLS-AA, with the first of these tested in conjunction with the TIP3P and TIP4P-Ew water models. In general, for both the amino acids and the small molecules, the tested force fields produce computed osmotic coefficients that are lower than experiment; this is indicative of excessively favorable solute-solute interactions. The sole exception to this general trend is provided by GROMOS54a7 when applied to amino acids: in this case, the computed osmotic coefficients are consistently too high. Importantly, we show that all of the force fields tested can be made to accurately reproduce the experimental osmotic coefficients of the amino acids when minor modifications-some previously reported by others and some that are new to this study-are made to the van der Waals interactions of the charged terminal groups. Special care is required, however, when simulating Proline with a number of the force fields, and a hydroxyl-group specific modification is required in order to correct Serine and Threonine when simulated with AMBER ff99SB-ILDN. Interestingly, an alternative parametrization of the van der Waals interactions in the latter force field, proposed by the Nerenberg and Head-Gordon groups, is shown to immediately produce osmotic coefficients that are in excellent agreement with experiment. Overall, this study reinforces the idea that osmotic coefficient measurements can be used to identify general shortcomings in commonly used force fields' descriptions of solute-solute interactions and further demonstrates that modifications to van der Waals parameters provide a simple route to optimizing agreement with experiment.

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Dataset Information

Reparameterization of Solute-Solute Interactions for Amino Acid-Sugar Systems Using Isopiestic Osmotic Pressure Molecular Dynamics Simulations.

Publications

Reparameterization of Solute-Solute Interactions for Amino Acid-Sugar Systems Using Isopiestic Osmotic Pressure Molecular Dynamics Simulations.

Similar Datasets

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