Differences between pair and bulk hydrophobic interactions.

Abstract

It is now well known that the pair interaction between two hydrocarbon molecules in water has distinctly different properties from the bulk hydrophobic interaction familiar to the biochemist, which is modeled by the transfer of a hydrocarbon from aqueous solutions to pure liquid hydrocarbon. We consider experimental data for pair interactions, which have been fitted by a simple empirical potential function, and point out some of their properties. (i) Surface free energy and cosphere overlap models, of the type considered until now, cannot reproduce correctly both the pair and bulk hydrophobic interactions. (ii) Pair interactions though still attractive are strikingly weaker in aqueous solution than in the gas phase, in contrast to the usual view of hydrophobic interactions. (iii) For pair interactions in water, the solvent-separated configuration is less important than the contact configuration if the hydrocarbon has more than two carbon atoms.Hydrophobic "bonding" involves the association of nonpolar groups in an aqueous environment. Kozak et al. (1) have drawn the distinction between bulk hydrophobic interactions-that is, "interactions involving large clusters of nonpolar groups as may, for instance, be found in the interior of a protein molecule"-and interactions between small numbers of nonpolar groups as may, for instance, be found at the surface of a protein molecule. These qualitatively different interactions are generally lumped together in the analysis of biochemical systems. For macromolecules, models of bulk hydrophobic interactions are appropriate for the buried molecular interior, while models for pair hydrophobic interactions are probably more appropriate at the molecular surface where there are many neighboring water molecules present. The distinction between these two kinds of interactions is important because they can be quite different in magnitude. As described below, the relative effect of water, in general, is to increase the bulk interaction and decrease the pair interaction for saturated hydrocarbons, although both are decreased for benzene. The macroscopic features of both bulk and pair hydrophobic interactions have been extensively studied and much is known about them (2-23). At the molecular scale a knowledge of aqueous hydrophobic interactions implies a knowledge of the potentials of average force between the hydrophobic species, and many questions about these potentials remain unanswered. For a complete understanding of these interactions in biochemical processes, we need a detailed knowledge of the forces involved. This paper presents some conclusions about the effects of water on bulk and pair interactions of hydrophobic molecules and suggests some tests of molecular scale models of these interactions. Pair Versus Bulk InteractionsThe relationships between pair interactions, bulk interactions, hydrophobic solvation, and the transfer of hydrophobic groups between water and hydrophobic medium is illustrated by the following thermodynamic cycle. nR(g, c@) AG,(g, Ce) IR (g co)H...

McMillan-Mayer theory of solutions revisited: Simplifications and extensions

“…Equation (1) has long been used 15,[25][26][27][28][29][30][31][32][33][34] by polymer, biopolymer, and colloid solution researchers to obtain molecular weights of macromolecules (from the first virial term c A k B T) and to study macromolecule solute-solute interactions (using the second virial term). The osmotic second virial coefficient has also been used in discussions of the hydrophobic interaction of small nonpolar solutes in water, [35][36][37][38][39] and we give an example in Sec. V. Unfortunately, the MM paper 1 is very hard to read and this is likely the main reason for the relative neglect of MM theory compared to KB theory.…”

A desolvation barrier to hydrophobic cluster formation may contribute to the rate‐limiting step in protein folding

“…2B, triangles) does not resemble the solvent contribution to the PMF; the barrier at intermediate solute separations is completely missed. The molecular surface and the solvent-accessible surface at the barrier are indicated schematically in Figure 3; the molecular surface is at a maximum because of the extended solvent-excluded region between the methanes, whereas the solvent-accessible surface is considerably less than that of the fully separated solutes (Wood & Thompson, 1990;Jackson & Sternberg, 1994). Simple potential functions used in protein folding studies often assume pair additivity of interactions between nonpolar groups (Sippl, 1995).…”

Hydrophobic Effect

“…It has to be kept in mind, however, that the pairwise interaction between small nonpolar molecules exhibits qualitative differences from the 'bulk' hydrophobic interaction, that is, the transfer of nonpolar solutes from water into a nonpolar phase (Wood and Thompson, 1990). For example, comparing second virial coefficients in the aqueous and gas phases one concludes that the contribution of water is unfavourable in the case of pairwise interactions, whereas it is favourable in the case of bulk transfers.…”