title: Dipeptide Aggregation in Aqueous Solution from Fixed Point-Charge Force Fields.
abstract: The description of aggregation processes with molecular dynamics simulations is a playground for testing biomolecular force fields, including a new generation of force fields that explicitly describe electronic polarization. In this work, we study a system consisting of 50 glycyl-l-alanine (Gly-Ala) dipeptides in solution with 1001 water molecules. Neutron diffraction experiments have shown that at this concentration, Gly-Ala aggregates into large clusters. However, general-purpose force fields in combination with established water models can fail to correctly describe this aggregation process, highlighting important deficiencies in how solute-solute and solute-solvent interactions are parametrized in these force fields. We found that even for the fully polarizable AMOEBA force field, the degree of association is considerably underestimated. Instead, a fixed point-charge approach based on the newly developed IPolQ scheme [Cerutti et al.J. Phys. Chem.2013,117, 2328] allows for the correct modeling of the dipeptide aggregation in aqueous solution. This result should stimulate interest in novel fitting schemes that aim to improve the description of the solvent polarization effect within both explicitly polarizable and fixed point-charge frameworks.
authors.affiliation: San Diego Supercomputer Center, University of California San Diego , 9500 Gilman Drive, La Jolla, California 92093, United States ; Department of Chemistry and Biochemistry, University of California San Diego , 9500 Gilman Drive, La Jolla, California 92093, United States.
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Götz
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego , 9500 Gilman Drive, La Jolla, California 92093, United States.
authors.forename: Denis
authors.initials: D
authors.lastname: Bucher
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego , 9500 Gilman Drive, La Jolla, California 92093, United States.
authors.forename: Steffen
authors.initials: S
authors.lastname: Lindert
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego , 9500 Gilman Drive, La Jolla, California 92093, United States ; Department of Pharmacology, University of California San Diego , 9500 Gilman Drive, La Jolla, California 92093, United States ; Howard Hughes Medical Institute, University of California San Diego , 9500 Gilman Drive, La Jolla, California 92093, United States.
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon