A quantum-mechanical framework for million-atom scale biological systems

Abstract Quantum-mechanical simulations provide the most fundamental description of matter, yet their computational cost commonly limits applications to systems containing at most thousands of atoms. Here, we present an all-electron quantum-mechanical framework focused on very fast calculations up to the multimillion-atom regime which is achieved by scaling down the accuracy of the framework while still maintaining agreement with experimental results. By combining algorithmically optimised Hartree-Fock with divide-and-conquer, using a minimal basis set and truncating long-range interactions, our approach efficiently handles million-atom structures while remaining accessible for smaller computation clusters and saving energy due to fast run times. We demonstrate this approach on very large biological systems, including a bacteriophage in water, totalling over 150 million electrons, representing, to our knowledge, the largest Hartree-Fock calculation performed to date. Our framework allows computing spectral data for DNA and drugs and enables protein structure assessments in strong agreement with structure evaluations by AlphaFold.