Polarizable Empirical Force Field for the Primary and Secondary Alcohol Series Based on the Classical Drude Model

Abstract

A polarizable empirical force field based on the classical Drude oscillator has been developed for the aliphatic alcohol series. The model is optimized with emphasis on condensed-phase properties and is validated against a variety of experimental data. Transferability of the developed parameters is emphasized by the use of a single electrostatic model for the hydroxyl group throughout the alcohol series. Aliphatic moiety parameters were transferred from the polarizable alkane parameter set, with only the Lennard-Jones parameters on the carbon in methanol optimized. The developed model yields good agreement with pure solvent properties with the exception of the heats of vaporization of 1-propanol and 1-butanol, which are underestimated by approximately 6%; special LJ parameters for the oxygen in these two molecules that correct for this limitation are presented. Accurate treatment of the free energies of aqueous solvation required the use of atom-type specific O alcohol -O water LJ interaction terms, with specific terms used for the primary and secondary alcohols. With respect to gas phase properties the polarizable model overestimates experimental dipole moments and quantum mechanical interaction energies with water by approximately 10 and 8 %, respectively, a significant improvement over 44 and 46 % overestimations of the corresponding properties in the CHARMM22 fixed-charge additive model. Comparison of structural properties of the polarizable and additive models for the pure solvents and in aqueous solution shows significant differences indicating atomic details of intermolecular interactions to be sensitive to the applied force field. The polarizable model predicts pure solvent and aqueous phase dipole moment distributions for ethanol centered at 2.4 and 2.7 D, respectively, a significant increase over the gas phase value of 1.8 D, whereas in a solvent of lower polarity, benzene, a value of 1.9 is obtained. The ability of the polarizable model to yield changes in dipole moment as well as the reproduction of a range of condensed phase properties indicates its utility in the study of the properties of alcohols in a variety of condensed phase environments as well as representing an important step in the development of a comprehensive force field for biological molecules.

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

“…This level of theory provides molecular geometries consistent with available gasphase experimental data and it has been previously utilized in the optimization of other small molecules with the Drude force field. 30,[32][33][34]53 QM calculations of the molecular electrostatic potentials (ESP) were performed on MP2-optimized geometries using the B3LYP hybrid functional [54][55][56] and the correlation-consistent double-zeta Dunning aug-cc-pVDZ basis set. 57 Single-point energy B3LYP calculations were performed with the tight convergence criteria producing the target QM ESP maps.…”

“…The use of different temperatures for the molecular volumes and heats of vaporization calculations on NMA was performed as previously discussed. 30 Free energies of hydration were also computed for the model compounds (Table IV). The free energies of hydration for NMA and ACEM are comparable to the experimental measurements.…”

“…The approach was proposed by Paul Drude in 1900 26 as a simple way to describe the dispersive properties of materials and introduced into CHARMM (Chemistry at HARvard Molecular Mechanics) back in 2003. 22,27 Ever since, force field parameters based on Drude oscillator models have been developed for water, 22,28 alkanes, 29 alcohols, 30 ethers, 31 amides, 32 aromatics, 33 nitrogen-containing heteroaromatics, 34 sulfur-containing compounds, 35,36 and ions. 37,38 Those for biomolecules, such as proteins, nucleic acids, lipids, and carbohydrates, 39 are under active development.…”

“…32 As described below the optimization was performed following standard protocols used for the Drude model in our laboratory. 23,24,[29][30][31] The final parameter set was then used in the KB analysis.…”

Opening and closing of the periplasmic gate in lactose permease

“…The initial configuration was submitted to 256 steps of conjugate-gradient energy minimization. In vacuo molecular dynamics simulations at constant temperature were conducted with NAMD 2.6 (30) using the CHARMM force field (31,32) and a time step of 1 fs. A 100-ns trajectory was run for each model.…”