Before revision:  Up until now , it has usually been cost prohibitive to determine the convergence of these calculations with respect to the size of the QM region. Recent advances in reformulating electronic structure algorithms for stream processors such as graphical processing units have made QM/MM calculations of optimized reaction paths with QM regions comprising up to O(10^3) atoms feasible. Here, we leverage these GPU-accelerated quantum chemistry methods to investigate catalytic properties in catechol O-methyltransferase  . Using QM regions ranging in size from the reactant only (63 atoms) up to nearly one-third of the entire protein (940 atoms), we show that convergence of properties such as the activation energy of the catalyzed reaction can be quite slow.
After revision:  Up until now , it has usually been cost prohibitive to determine the convergence of these calculations with respect to increasingly large QM regions. Leveraging recent advances in electronic structure efficiency and accuracy, we investigate catalytic properties in catechol O-methyltransferase . Using QM regions ranging in size from the reactant only (63 atoms) up to nearly one-third of the entire protein (940 atoms), we show that convergence of properties such as the activation energy of the catalyzed reaction can be quite slow.