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. 2024 Feb 13;20(3):1293-1305.
doi: 10.1021/acs.jctc.3c01171. Epub 2024 Jan 19.

A Fast, Convenient, Polarizable Electrostatic Model for Molecular Dynamics

Liangyue Wang  1 , Michael Schauperl  2 , David L Mobley  3 , Christopher Bayly  4 , Michael K Gilson  5
Affiliations

A Fast, Convenient, Polarizable Electrostatic Model for Molecular Dynamics

Liangyue Wang et al. J Chem Theory Comput. .

Abstract

We present an efficient polarizable electrostatic model, utilizing typed, atom-centered polarizabilities and the fast direct approximation, designed for efficient use in molecular dynamics (MD) simulations. The model provides two convenient approaches for assigning partial charges in the context of atomic polarizabilities. One is a generalization of RESP, called RESP-dPol, and the other, AM1-BCC-dPol, is an adaptation of the widely used AM1-BCC method. Both are designed to accurately replicate gas-phase quantum mechanical electrostatic potentials. Benchmarks of this polarizable electrostatic model against gas-phase dipole moments, molecular polarizabilities, bulk liquid densities, and static dielectric constants of organic liquids show good agreement with the reference values. Of note, the model yields markedly more accurate dielectric constants of organic liquids, relative to a matched nonpolarizable force field. MD simulations with this method, which is currently parametrized for molecules containing elements C, N, O, and H, run only about 3.6-fold slower than fixed charge force fields, while simulations with the self-consistent mutual polarization average 4.5-fold slower. Our results suggest that RESP-dPol and AM1-BCC-dPol afford improved accuracy relative to fixed charge force fields and are good starting points for developing general, affordable, and transferable polarizable force fields. The software implementing these approaches has been designed to utilize the force field fitting frameworks developed and maintained by the Open Force Field Initiative, setting the stage for further exploration of this approach to polarizable force field development.

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Conflict of interest statement

The authors declare the following competing financial interest(s): M.K.G. has an equity interest in and is a cofounder and scientific advisor of VeraChem LLC. He is also on the Scientific Advisory Boards of Denovicon and In Cerebro. D.L.M. serves on the scientific advisory boards of OpenEye Scientific Software, Cadence Molecular Sciences, and Anagenex, and is an Open Science Fellow with Psivant Sciences.

Figures

Figure 1
Figure 1
Diagram of the Factor-Pol toolkit used to carry out QM calculations, derive optimized, typed polarizabilities and polarization-adapted BCCs, and assign RESP-dPol and AM1-BCC-dPol charges, and polarizabilities to molecules.
Figure 2
Figure 2
Comparison of gas-phase molecular dipole moments (Debye) computed with the AM1-BCC-dPol electrostatics model with QM reference results for element-based polarizabilities (a) and Sage LJ type-based polarizabilities (b).
Figure 3
Figure 3
Comparison of molecular polarizabilities computed from our atomic polarizabilities against experimental reference data, for element-based polarizabilities (a) and Sage LJ type-based polarizabilities (b).
Figure 4
Figure 4
Two conformers of alanine dipeptide used to examine the transferability of charges trained for one conformation and tested on a second conformation (see Table 2).
Figure 5
Figure 5
Comparison of computed and experimental mass densities (g/mL) for simulations with the AM1-BCC fixed-charge model (a) and with our AM1-BCC-dPol electrostatic model using element-based polarizabilities (b) and Sage LJ-based polarizabilities (c).
Figure 6
Figure 6
Comparisons of computed and experimental inverse relative dielectric constants (1/D), for simulations with the AM1-BCC fixed-charge model (a) and with our AM1-BCC-dPol electrostatic model using element-based polarizabilities (b) and Sage LJ-based polarizabilities (c).
See this image and copyright information in PMC

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