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.