An efficient electrostatic embedding QM/MM method using periodic boundary conditions based on particle-mesh Ewald sums and electrostatic potential fitted charge operators

TL;DR

This paper introduces a fast and efficient electrostatic embedding QM/MM method using periodic boundary conditions, particle-mesh Ewald sums, and fitted charges, enabling accurate simulations of large biological systems.

Contribution

The authors develop a novel QM/MM approach combining ESPF charges and PME sums that is computationally efficient for large periodic biological systems.

Findings

Accurately reproduces experimental absorption maximum of cryptochrome 1

Efficiently treats systems with around 93,000 atoms

Demonstrates applicability to large biological molecules

Abstract

Hybrid quantum mechanics / molecular mechanics (QM/MM) models successfully describe the properties of biological macromolecules. However, most QM/MM methodologies are constrained to unrealistic gas phase models, thus limiting their applicability. In the literature, several works have attempted to define a QM/MM model in periodic boundary conditions (PBC) but frequently the models are too time-consuming for general applicability to biological systems in solution. Here, we define a simple and efficient electrostatic embedding QM/MM model in PBC combining the benefits of electrostatic potential fitted (ESPF) atomic charges and particle-mesh Ewald sums, that can efficiently treat systems of arbitrary size at a reasonable computational cost. To illustrate this, we apply our scheme to extract the lowest singlet excitation energies from a model for arabidopsis thaliana cryptochrome 1 containing circa 93000 atoms, reproducing accurately the experimental absorption maximum.