Multibody correlations in the hydrophobic solvation of glycine peptides

Protein collapse during folding is often assumed to be driven by a hydrophobic solvation energy (ΔG_vdw) that scales linearly with solvent-accessible surface area (A). In a previous study, we argued that ΔG_vdw, as well as its attractive (ΔG_att) and repulsive (ΔG_rep) components, was not simply a linear function of A. We found that the surface tensions, γ_rep, γ_att, and γ_vdw, gotten from ΔG_rep, ΔG_att, and ΔG_vdw against A for four configurations of deca-alanine differed from those obtained for a set of alkanes. In the present study, we extend our analysis to fifty decaglycine structures and atomic decompositions. We find that different configurations of decaglycine generate different estimates of γ_rep. Additionally, we considered the reconstruction of the solvation free energy from scaling the free energy of solvation of each atom type, free in solution. The free energy of the isolated atoms, scaled by the inverse surface area the atom would expose in the molecule does not reproduce the γ_rep for the intact decaglycines. Finally, γ_att for the decaglycine conformations is much larger in magnitude than those for deca-alanine or the alkanes, leading to large negative values of γ_vdw (-74 and -56 cal/mol/Ų for CHARMM27 and AMBER ff12sb force fields, respectively). These findings imply that ΔG_vdw favors extended rather than compact structures for decaglycine. We find that ΔG_rep and ΔG_vdw have complicated dependencies on multibody correlations between solute atoms, on the geometry of the molecular surface, and on the chemical identities of the atoms.