2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 45(2011) N 2 p. 309-317;
Y.N. Vorobjev*

Molecular Dynamics Method for Proteins with Ionization-Conformation Coupling and Equilibrium Titration

Institute of Chemical biology and Fundamental Medicine of Siberian Branch of Russian Academy of Sciences, Novosibirsk, 630090 Russia

Received - 2010-04-09; Accepted - 2010-05-25

A new realization of the constant pH molecular dynamics simulation is proposed in mean force potential of proton reservoir in constant titration conditions. The MD-pH-ET method is used for a protein in the most probable ionization microstate, which is the state with minimal energy of the current conformation taking into account the correcting ionization potential of mean force considering an equilibrium ensemble of ionization states. The new MD-pH-ET method allows one to carry out an optimization of protein structure and the total free energy of a protein in the aqueous solution at constant pH and to calculate the pH-dependent properties. The MD-pH-ET method possesses the following unique features: (1) it uses the most precise and computationally effective realization of calculation of electrostatic energy of a protein in aqueous solution, the model of continuous dielectric media with Poisson equation, and the generalized Born method with "ideal" Born atomic radii; (2) it uses the same model of the potential energy surface in the ionization-conformation phase space both for calculating the potential energy of the protein and atomic forces and for determining the most probable ionization states; (3) it calculates the total free energy of the protein in the aqueous solution in a proton reservoir under the conditions of equilibrium titration. The workability of the new method MD-pH-ET is demonstrated for a molecule of the BPTI protein.

molecular modeling, constant pH molecular dynamics, solvation, electrostatics, potential of mean force, equilibrium titration