title: Temperature dependence of three-body hydrophobic interactions: potential of mean force, enthalpy, entropy, heat capacity, and nonadditivity.
abstract: Temperature-dependent three-body hydrophobic interactions are investigated by extensive constant-pressure simulations of methane-like nonpolar solutes in TIP4P model water at six temperatures. A multiple-body hydrophobic interaction is considered to be (i) additive, (ii) cooperative, or (iii) anti-cooperative if its potential of mean force (PMF) is (i) equal to, (ii) smaller than, or (iii) larger than the corresponding pairwise sum of two-methane PMFs. We found that three-methane hydrophobic interactions at the desolvation barrier are anti-cooperative at low to intermediate T, and vary from essentially additive to slightly cooperative at high T. Interactions at the contact minimum are slightly anti-cooperative over a wider temperature range. Enthalpy, entropy, and heat capacity are estimated from the computed PMFs. Contrary to the common expectation that burial of solvent-accessible nonpolar surface area always leads to a decrease in heat capacity, the present results show that the change in heat capacity upon three-methane association is significantly positive at the desolvation barrier and slightly positive at the contact minimum. This suggests that the heat capacity signature of a hydrophobic polymer need not vary uniformly nor monotonically with conformational compactness. Ramifications for protein folding are discussed.
authors.affiliation: Protein Engineering Network of Centres of Excellence, Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Maria Sabaye
authors.initials: MS
authors.lastname: Moghaddam
authors.forename: Seishi
authors.initials: S
authors.lastname: Shimizu
authors.forename: Hue Sun
authors.initials: HS
authors.lastname: Chan
mesh_terms: D019277:Entropy; D057927:Hydrophobic and Hydrophilic Interactions; D008697:Methane / Q000737:chemistry*; D017510:Protein Folding; D013696:Temperature
chemical_list: D008697:Methane