QUICK and Robust ESP and RESP Charges for Computational Biochemistry: Open-Source GPU Implementation

We
describe the implementation details of highly efficient ab
initio electrostatic potential (ESP) calculations on
graphics processing units (GPUs) and introduce a novel scheme for
partial charges that are robust against molecular orientation. Performance
analyses are discussed, and we highlight that in our new implementation,
a single data center GPU can outperform 128 corresponding data center
CPU cores in time to solution. This implementation in the open-source
Quantum Interaction Computational Kernel code (QUICK) enables ESP
computations on highly dense grids that surpass what is reported in
the literature, on the order of Ngrid points ∼ 20000 points/atom. We demonstrate that, in this dense-grid
limit, ESP charges become independent of molecular orientation. We
denote such ESP charges as being robust against molecular
orientation and validate this desirable attribute against standard
charge schemes. Our proposed charge scheme, called reweighted RESP
(rwRESP), is designed to significantly overcome the sensitivity to Ngrid points that limits the reliability
of canonical RESP charges. By effectively amending this Ngrid points-sensitivity, we demonstrate that rwRESP
charges also achieve robustness against molecular orientation. Ultradense-grid
ESP computations and rwRESP fits can be readily performed via the
seamless integration of QUICK with AmberTools, enabling highly efficient
and reliable parametrization of the general AMBER force field (GAFF)
for nonstandard residues. In this spirit, we believe that our fully
fledged GPU protocol for obtaining robust molecular charges will facilitate
a wide range of applications, such as high-throughput parametrization
of molecular interaction potentials, while also serving as a foundational
step toward GPU-accelerated on-the-fly polarizable QM/MM simulations
with QUICK.