Polarizable empirical force field for nitrogen‐containing heteroaromatic compounds based on the classical Drude oscillator

Abstract

The polarizable empirical CHARMM force field based on the classical Drude oscillator has been extended to the nitrogen-containing heteroaromatic compounds pyridine, pyrimidine, pyrrole, imidazole, indole and purine. Initial parameters for the 6-membered rings were based on benzene with non-bond parameter optimization focused on the nitrogen atoms and adjacent carbons and attached hydrogens. In the case of 5-member rings, parameters were first developed for imidazole and transferred to pyrrole. Optimization of all parameters was performed against an extensive set of quantum mechanical and experimental data. Ab initio data was used for determination of the initial electrostatic parameters, the vibrational analysis, and in the optimization of the relative magnitudes of the Lennard-Jones parameters, through computations of the interactions of dimers of model compounds, model compound-water interactions and interactions of rare gases with model compounds. The absolute values of the Lennard-Jones parameters were determined targeting experimental heats of vaporization, molecular volumes, heats of sublimation, crystal lattice parameters and free energies of hydration. Final scaling of the polarizabilities from the gas phase values by 0.85 was determined by reproduction of the dielectric constants of pyridine and pyrrole. The developed parameter set was extensively validated against additional experimental data such as diffusion constants, heat capacities and isothermal compressibilities, including data as a function of temperature.

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 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.…”

Mg2+/Ca2+ binding to DNA bases: a quantum chemical method and ABEEMσπ/MM fluctuating charge model study

“…In the classical Drude oscillator model, also known as the ''shell'' or ''charge on spring'' model, the polarizability is introduced via the inclusion of a single auxiliary charge (Drude) particle attached to each non-hydrogen atom by a harmonic spring. It is noteworthy that the CHARMM Drude PFF has been successfully developed for a wide range of systems encompassing water [56,57], ions [58], and organic molecules [59][60][61][62], especially for the significant progress for nucleic acid bases by Baker and Anisimov et al [63] most recently. The fluctuating charge models introduce polarizability into standard energy functions by allowing the values of the partial charges to respond to the electric field of their environment, thereby altering the molecular polarizability [64,65].…”

Polarizable Atomic Multipole-Based Molecular Mechanics for Organic Molecules

“…9,31–35 Detailed discussions of the various polarization models can be found in recent reviews of polarizable force field development. 36–40 The performance of different approaches in accounting for polarization has been compared in the study of ion and small molecule interactions. 41,42 The modeling of neat organic liquids, including alcohols, acids, amides and aromatics, has also been reported using polarizable potentials.…”