This dissertation is composed of three parts. The first part is to argue the solvent
effects on the solvatochromic shift of the n ! !* excitation of acetone in ambient and
supercritical water fluid using a hybrid QM!CI/MM potential in MC simulations. The
solute is described by the AM1 approach and water molecules are treated classically.
Specially, the spontaneous polarization of the solvent due to the excitation of the solute
was considered. The solvent effects on the blue shift of acetone in water fluids at various
temperatures and solvent densities are examined.
The second part is to investigate the role of dopa decarboxylase (DDC) in the
catalysis of converting anti-Parkinson drug L-dopa into dopamine. By means of
combined QM/MM potentials in MD simulations, we first analyze the factors
contributing to the tautomeric equilibrium of an intramolecular proton transfer in the
external PLP!L-dopa aldimine (the Michaelis complex). How the intrinsic properties,
solvent effects as well as the enzyme environment control the shift of the equilibrium is
discussed. Afterward, the free energy profiles for the decarboxylations of the external
aldimines both in water and in DDC are calculated. The contributions of DDC to the rate
enhancement of the reaction are elucidated. The reaction mechanism of L-dopa
decarboxylation in DDC is proposed.
The third part is to study the structural dynamics of lysine-specific demethylase
(LSD1) in complex with CoREST and protein-substrate interactions of LSD1 with
histone H3 tail. MD simulations of LSD1•CoREST complex bound to a 16 a.a. of the Nterminal
H3-tail peptide (H3-p16) were carried out using NAMD to study the
conformational flexibility of the protein complex, especially the substantial oscillation of
the TOWER domain. In addition, the simulations reveal some important protein-peptide
and peptide-peptide interactions between LSD1 and H3-p16 that are absent in the crystal