title: Quantification of the hydrophobic interaction by simulations of the aggregation of small hydrophobic solutes in water.
abstract: The hydrophobic interaction, the tendency for nonpolar molecules to aggregate in solution, is a major driving force in biology. In a direct approach to the physical basis of the hydrophobic effect, nanosecond molecular dynamics simulations were performed on increasing numbers of hydrocarbon solute molecules in water-filled boxes of different sizes. The intermittent formation of solute clusters gives a free energy that is proportional to the loss in exposed molecular surface area with a constant of proportionality of 45 +/- 6 cal/mol A(2). The molecular surface area is the envelope of the solute cluster that is impenetrable by solvent and is somewhat smaller than the more traditional solvent-accessible surface area, which is the area transcribed by the radius of a solvent molecule rolled over the surface of the cluster. When we apply a factor relating molecular surface area to solvent-accessible surface area, we obtain 24 cal/mol A(2). Ours is the first direct calculation, to our knowledge, of the hydrophobic interaction from molecular dynamics simulations; the excellent qualitative and quantitative agreement with experiment proves that simple van der Waals interactions and atomic point-charge electrostatics account for the most important driving force in biology.
authors.affiliation: Stanford University School of Medicine, Department of Structural Biology, Fairchild Building, Room D-109, Stanford, CA 94305, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Raschke
authors.forename: J
authors.initials: J
authors.lastname: Tsai
authors.forename: M
authors.initials: M
authors.lastname: Levitt
mesh_terms: D003198:Computer Simulation; D004735:Energy Transfer; D008697:Methane / Q000737:chemistry; D008958:Models, Molecular; D012996:Solutions / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D012996:Solutions; D012997:Solvents; D014867:Water; D008697:Methane