A Potential Improvement for Electrostatic Interactions: Constructing A Fluctuating Charge Model for Nucleic Acids

Given the recent and ongoing increases in computational resources for simulating large biomolecules, and the variety of complex environments researchers wish to study these systems in, it is worth examining how conventional molecular mechanics algorithms could be improved upon by including interactions that are historically neglected. Specifically, traditional fixed charge based force fields struggle to quantitatively describe the extent to which interactions are driven by electrostatic polarization or charge transfer. As such, we will present our approach to augmenting AMBER based force fields for nucleic acids with the ability to account for polarization. Within our model, the traditionally fixed charges are allowed to adjust to a molecules geometry and environment via an electron density based fluctuating charge model. With the aid of density functional theory calculations of small oligonucleotides, we examine how the inclusion of polarization effects by explicitly describing electron populations could improve the description of electrostatically driven interactions such as hydrogen bonding or charge transfer in gas-phase simulations.