Kirkwood-Buff analysis of aqueous N-methylacetamide and acetamide solutions modeled by the CHARMM additive and Drude polarizable force fields

Abstract

Kirkwood-Buff analysis was performed on aqueous solutions of N-methylacetamide and acetamide using the Chemistry at HARvard Molecular Mechanics additive and Drude polarizable all-atom force fields. Comparison of a range of properties with experimental results, including Kirkwood-Buff integrals, excess coordination numbers, solution densities, partial molar values, molar enthalpy of mixing, showed both models to be well behaved at higher solute concentrations with the Drude model showing systematic improvement at lower solution concentrations. However, both models showed difficulties reproducing experimental activity derivatives and the excess Gibbs energy, with the Drude model performing slightly better. At the molecular level, the improved agreement of the Drude model at low solute concentrations is due to increased structure in the solute-solute and solute-solvent interactions. The present results indicate that the explicit inclusion of electronic polarization leads to improved modeling of dilute solutions even when those properties are not included as target data during force field optimization.

Experimental Atom-by-Atom Dissection of Amide–Amide and Amide–Hydrocarbon Interactions in H2O

“…58 CHARMM radial distributions for the two sp 3 C unified atoms of nma, one bonded to the amide C and the other to the amide N are very similar, revealing little if any context-dependence of the interactions of these sp 3 C atoms of one nma with sp 3 C, sp 2 O and sp 2 N atoms of another nma. Some context dependence could be present for sp 3 C – water sp 2 O interactions.…”

“…58 From the published graphical results, we obtain estimates of μ 22 ex /2 for these force fields (Table S12). For CHARMM, μ 22 ex /2 = – 40 cal mol −1 molal −1 , while for Drude μ 22 ex /2 = 16 cal mol −1 molal −1 .…”

Current Status of Protein Force Fields for Molecular Dynamics Simulations

“…(69) and a final set by Lin et al . (110) In the latest model LJ parameters were selected to give acceptable intramolecular hydrogen bond distances in α-helix conformations of alanine polypeptides in addition to allowing reproduction of NMA experimental condensed phase properties (110). CMAP corrections for alanine dipeptide were also used to allow the ( ϕ, ψ ) Ramachandran map to reproduce a high-level QM (RIMP2/CBS//RIMP2/cc-pVDZ) surface, where the CBS (complete basis set) extrapolation was obtained from RIMP2/cc-pVTZ and RIMP2/cc-pVQZ single point energies following the prescription of Halkier et al .…”

A GROMOS-Compatible Force Field for Small Organic Molecules in the Condensed Phase: The 2016H66 Parameter Set

“…The calculated values for the alcohols, the ketones, the carboxylic acids, the other amines, the amides and the disulfide are systematically underestimated compared to the experimental ones.The deviation is particularly large for the amides AMD, LNMA and DAMD, characterized by anomalously high experimental permittivities of 128 65.0, 139.5 and 37.8, respectively, reason for which their representative points are not displayed inFigure 3.The corresponding values calculated using 2016H66 are significantly lower, namely 30.3, 49.0 and 20.2, respectively. Note that the representation of amides and in particular of their dielectric properties within classical force fields is a challenging problem that has attracted considerable attention over the years 95,[208][209][210][211][212]. .…”