Density functional theory studies of biochemical hydrolysis reactions and physical mechanisms of ATP energy transfer

We apply electronic structure methods, namely Kohn Sham density functional theory (KS-DFT), to study the hydrolysis reaction of adenosine triphosphate (ATP), the molecule responsible for energy storage and transport in all living things. Similarly, the hydrolysis of Benzo[a]pyrene diol epoxide (BPDE), a carcinogenic molecule present in tobacco smoke, is studied, due to its role in detoxification. Using these methods, we find geometric structures, vibrational modes, and thermodynamic parameters that give insight into the free energy at various stages of these reactions. In addition to computing the free energy released upon hydrolysis of ATP to ADP, we quantize the vibrational modes of ADP to develop a phonon-based model for the transfer of this energy to a macromolecule. From this, we determine important vibrational modes for energy transfer, an approximate timescale for energy transfer, and develop a useful theoretical framework that can be further extended in the future. In the BPDE hydrolysis reaction, we find energies and structures of transition states associated with spontaneous and general acid catalyzed hydrolysis reactions. To do so, we performed a variety of optimizations and energy surface scans. As an intermediate to the hydrolysis reaction, we found a hydrogen bonded BPDE-acid complex that is formed prior to the transition state. We additionally characterized this complex for BPDE hydrogen bonded to four different acids and water. These hydrogen bonded complexes must satisfy two apparently contradictory requirements: their energies must decrease relative to the reactants, and their Gibbs free energies must increase. We show that both of these requirements can be fulfilled because of a decrease in entropy associated with hydrogen bonding that can be accurately accounted for with estimates of various associated vibrational motions. We also analyze the results in terms of electronic energy and translational, rotational, and vibrational entropy. The interplay between various free energy components allows for both an energetically and thermodynamically consistent reaction intermediate