Reactive Simulations for Biochemical Processes

Abstract

After a brief review of the hybrid QM/MM molecular dynamics scheme and its coupling to the metadynamics method, I will show how such a combination of computational tools can be used to study chemical reactions of general biological interest. Specifically, by using such a reactive hybrid paradigm, where the QM driver is a Car–Parrinello Lagrangian dynamics, we have inspected the ATP hydrolysis reaction in the anti-freezing protein known as heat shock cognate protein (Hsc70) and the unconventional propagation of protons across peptide groups in the H-path of the bovine cytochrome c oxidase. While the former represents a fundamental reaction operated by all living beings in a wealth of processes and functions, the second one is involved in cell respiration. For both systems accurate X-ray data are available, yet the actual reaction mechanism escapes experimental probes. The simulations presented here provide the complementary information missing in experiments, offer a direct insight into the reaction mechanisms at a molecular level, and allow to understand which pathways nature can follow to realize these processes fundamental to living organisms.