Accessible Surface and Thermodynamics of Hydration

Lee and Richards (1971) defined the solvent-accessible surface as that described by the center of a solvent molecule rolled about the surface of a solute molecule. This concept and its offspring are the basis of various computations of the contribution of hydration to the thermodynamics of protein folding and the thermodynamics of protein interactions. Ed-sall and McKenzie (1983) reviewed the literature on the thermodynamics of transfer processes used to model hydration and correlated this information with protein structure results analyzed according to the Lee and Richards formalism. Other notable reviews are those by Richards (1977), Nemethy et al. (1981), and Nemethy (1986). 

There have been several refinements in the Lee and Richards algorithm and its use. Wodak and Janin (1980) developed an approximate function, and Richmond (1984) developed an exact analytical function for the solvent-accessible surface. Both functions can be coded for machine computation. Richmond (1984) drew attention to the relationship between accessible surface and excluded volume. 

The simplest use of an estimate of the solvent-accessible surface is the specification of a residue as exposed or buried, depending on whether 

Atomic and group additivity schemes, derived from solvent accessibility calculations and measurements on model systems, have been used to estimate the thermodynamics of hydration of proteins and peptides (Eisenberg and McLachlan, 1986 Ooi and Oobatake, 1988a Ooi et al., 1987). 

Ben-Naim et al. (1989a) provided a theoretical framework for separating the solvation thermodynamics into their several components (1) hard-core interactions, which depend on the volume of the solute and the cost of making a cavity in the solvent and (2) interactions of the 

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