Role of electrostatics in modulating hydrophobic interactions and barriers to hydrophobic assembly.

Abstract

Hydrophobic effects continue to be an active area of research due to implications for a wide range of physicochemical phenomena. Molecular dynamics simulations have been used extensively in the study of such effects using various water potential models, with few studies addressing the differences between models. In particular, studies considering the explicit treatment of water polarizability are underrepresented in the literature. We present results from molecular dynamics simulations that systematically compare the dependence of large-scale hydrophobic effects on the water model. We consider three common nonpolarizable models (SPC/E, TIP3P, and TIP4P) and two common polarizable models (TIP4P-FQ and SWM4-NDP). Results highlight the similarities and differences of the different water models in the vicinity of two large hydrophobic plates. In particular, profiles of average density, density fluctuations, orientation, and hydrogen bonding show only minor differences among the water models studied. However, the potential of mean force for the hydrophobe dimerization is significantly reduced in the polarizable water systems. TIP4P-FQ shows the deepest minimum of approximately -54(+/-3) kcal/mol compared to -40(+/-3), -40(+/-2), -42(+/-3), and -45(+/-5) kcal/mol for TIP4P, TIP3P, SPC/E, and SWM4-NDP (all relative to the dissociated state). We discuss the relationship between hydrophobic association and the strength of water-water interactions in the liquid phase. Results suggest that models treating polarizability (both implicitly and explicitly) influence a stronger driving force toward hydrophobic assembly. Implications of these results, as well as prospectives on future work, are discussed.