Research using various types of multiscale enzyme simulations has inarguably provided answers to “grand challenge” questions in chemistry and biochemistry, especially using QM/MM, ONIOM, or QM-only cluster models. Despite decades of calibration studies and comparisons of QM and QM/MM results, a dearth of published, algorithmic guidelines or online tutorials exists. The quantitative relationships between composition or size of the active site/QM region and computational accuracy are still poorly understood. Calibration studies of enzyme thermodynamics/kinetics usually employ only 2-15 different enzyme models, and like published applications of QM-cluster models, they frequently lack reproducible structural data. Development of a software toolkit called RINRUS (Residue Interaction Network ResidUe Selector) has allowed calibration of QM-cluster models on an unprecedented, fine-grained scale. By generating hundreds of unique QM-cluster models from 120 – 530 atoms in size, the convergence of thermodynamic and kinetic properties of the Catechol-<i>O</i>-methyl transferase (COMT) enzyme is analyzed. Our data will be incorporated into a reproducible and systematic rules-based approach for designing QM and QM/MM mechanistic studies of enzymes.<br/>

Reproducible, rational, and rigorous QM-cluster enzyme models

2019 Fall National Meeting

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