Application of the QM/MM molecular dynamics method to the enzymatic deamination of cytidine

PHYS 426

Toshiaki Matsubara, matsu05@hiroshima-u.ac.jp and Misako Aida. Graduate School of Science, Hiroshima University, 1-3-1, Kagamiyama, Higashi-Hiroshima, 739-8530, Japan
We developed the quantum mechanics (QM) + molecular mechanics (MM) (ONIOM) molecular dynamics (MD) method to simulate the real enzymatic reaction. This method, in which the equation of motion for the nucleus of the molecular system is solved in the QM/MM hybrid force field, makes the simulation of the real reaction of the enzyme possible. We applied our method to the hydrolytic deamination of cytidine by cytidine deaminase, which plays an important role inside the human body to activate the anticancer drug. The QM/MM-MD simulations were performed at the {HF/3-21G:AMBER99+TIP3P} level with a constant temperature, treating the active site including the substrate by the QM method and the other by the MM method. The water molecules were placed around cytidine deaminase to simulate the water solvent. The simulations showed that the amino acid residues in the active site significantly contribute to the catalysis through the interaction with the substrate.
 

Poster Session
7:30 PM-10:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster

Division of Physical Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006