Quantum and classical dynamics simulations of ATP hydrolysis in solution

ATP hydrolysis is a key reaction in living cells that drives many cellular processes. The reaction, which involves gamma phosphate cleavage from ATP, converting it to ADP, has been suggested to occur via an associative or dissociative mechanism dependent upon the surrounding environment. Prior quantum chemical studies suffered from short simulation time scales failing to capture free energy contributions due to relaxation of the surrounding aqueous environment. We have developed a highly parallelized QM/MM implementation in the NAMD and OpenAtom simulation packages, using the dual grid, dual length scale method for combined plane-wave and Euler exponential spline-based QM/MM simulations. This approach, using message-driven parallel quantum and classical dynamics, permits sufficient time scale simulations for quantum chemical events such as ATP hydrolysis and is found to accurately and reliably include the free energy contributions of solvent relaxation to hydrolysis. In this paper, we describe the application of the dual grid, dual length plane-wave-based QM/MM method to study both the associative and dissociative mechanisms of ATP hydrolysis, accounting for the free energy contribution from solvent relaxation, as well as for the key role of Mg ²⁺ in the reaction.