Accelerating reliable multiscale quantum refinement of protein-drug systems enabled by machine learning.

ABSTRACT: Biomacromolecule structures are essential for drug development and biocatalysis. Quantum refinement (QR) methods, which employ reliable quantum mechanics (QM) methods in crystallographic refinement, showed promise in improving the structural quality or even correcting the structure of biomacromolecules. However, vast computational costs and complex quantum mechanics/molecular mechanics (QM/MM) setups limit QR applications. Here we incorporate robust machine learning potentials (MLPs) in multiscale ONIOM(QM:MM) schemes to describe the core parts (e.g., drugs/inhibitors), replacing the expensive QM method. Additionally, two levels of MLPs are combined for the first time to overcome MLP limitations. Our unique MLPs+ONIOM-based QR methods achieve QM-level accuracy with significantly higher eff

SUBMITTER: Yan Z 

PROVIDER: S-EPMC11099068 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature