A Complete Thermodynamic Characterization of Electrostatic and Hydrophobic Associations in the Temperature Range 0 to 100 degrees C from Explicit-Solvent Molecular Dynamics Simulations

作者：Zhu Shun; Elcock Adrian H^*

来源：Journal of Chemical Theory and Computation, 2010, 6(4): 1293-1306.

DOI：10.1021/ct1000704

The electrostatic and hydrophobic interactions that dominate the behavior of proteins and other biomolecules exhibit fundamentally different thermodynamic characteristics, and the correct reproduction of these differences is likely to be an important requirement for models that aim to predict the thermodynamics of protein stability and protein protein interactions. To assess the abilities of some current models to capture these differences, we report here the results of molecular dynamics (MD) simulations examining the association of acetate-methyl-ammonium and methane-methane pairs at 11 different temperatures from - 12.5 to 112.5 degrees C. Simulations were performed using two popular water models (TIP3P and TIP5P), with a total simulation time of 22 mu s. With both water models, we find that the acetate-methylammonium salt-bridge interaction is significantly more stabilized by high temperatures (e.g., over the range 25 to 100 degrees C) than is the methane-methane hydrophobic interaction. At low temperatures however, the two models exhibit quite different behavior, with the TIP5P model predicting little change in the relative stabilities of the two types of interaction in the range - 12.5 to 50 degrees C; this surprising result has potential implications for understanding adaptation to life in psychrophilic organisms. Fitting the Delta G data to the Gibbs-Helmholtz equation allows the Delta H, Delta S, and Delta C(p) of interaction to be obtained, thereby yielding a complete thermodynamic characterization of the different types of interaction in the temperature range 0 to 100 degrees C: despite significant quantitative differences, both water models correctly capture the opposite signs of the Delta C(p) of electrostatic and hydrophobic interactions. Finally, we show that at high temperatures a Poisson-based continuum solvation model provides good agreement with the explicit-solvent MD results, but only when the atomic radii used in the continuum calculations are scaled with temperature.

• 出版日期2010-4