Book of Abstracts: Albany 2011
June 14-18 2011
©Adenine Press (2010)
Method of Molecular Dynamics for Proteins in the Ionization-Conformation Phase Space at Equilibrium Conditions at Constant pH
In view of the extensive interest in molecular dynamics simulations (1-4), a new realization of the constant-pH molecular dynamics simulation method (5) is proposed. Molecular dynamics simulation is performed in the potential of mean force of protein molecule in the water-proton bath at equilibrium titration conditions (MD-pH-ET). It is shown that: i) the algorithm of MD-pH-ET which delivers the highest numerical accuracy of the MD-pH-ET method, is the simulation of protein in its instant most probable physical ionization microstate with additional potential of mean force of equilibrium titration, which depends on a deviation of the most probable physical ionization microstate from an equilibrium ensemble of ionization microstates for a given protein conformation; ii) the new method MD-pH-ET allows one to carry out the optimization of protein structure and the total free energy of a protein in the aqueous solution at constant pH, and the calculation of the pH-dependent properties. Method MD-pH-ET possesses unique features such as: i) it uses precise and computationally effective realization of calculation of ionization equilibrium and electrostatic energy and atomic forces for protein in water solution by the model of continuous dielectric media with Poisson equation solved by the Fast Adaptive Multigrid Boundary Element (FAMBE) method (6). Coupling of FAMBE method with Generalized Born method by definition of the Poisson “ideal” Born atomic radii (7) allows one to accelerate an accurate calculation of forces and energies in the MD-pH-ET method; ii) it uses the same model of the potential energy surface in the ionization-conformational phase space, both for the calculation of the potential energy of the protein and atomic forces and for determining the ionization states; iii) it calculates the total free energy of the protein in the aqueous solution in proton reservoir under the conditions of equilibrium titration. The workability of the new method MD-pH-ET is demonstrated on a set of proteins.
This research has been supported by grant of Russian Fond of Basic Research #09-04-00136 and by projects #09-26 and # 09-119 of the Siberian Brunch of the RAS.
Institute of Chemical Biology and Fundamental Medicine