Intramolecular Interactions Overcome Hydration to Drive the Collapse Transition of Gly₁₅

Abstract

Simulations and experiments show oligo-glycines, polypeptides lacking any side chains, can collapse in water. We assess the hydration thermodynamics of this collapse by calculating the hydration free energy at each of the end points of the reaction coordinate, here taken as the end-to-end distance (r) in the chain. To examine the role of the various conformations for a given r, we study the conditional distribution, P(Rg|r), of the radius of gyration for a given value of r. The free energy change versus Rg, −kBT ln P(Rg|r), is found to vary more gently compared to the corresponding variation in the excess hydration free energy. Using this observation within a multistate generalization of the potential distribution theorem, we calculate a tight upper bound for the hydration free energy of the peptide for a given r. On this basis, we find that peptide hydration greatly favors the expanded state of the chain, despite primitive hydrophobic effects favoring chain collapse. The net free energy of collapse is seen to be a delicate balance between opposing intrapeptide and hydration effects, with intrapeptide contributions favoring collapse.

Characterizing Solvent Density Fluctuations in Dynamical Observation Volumes

“…We thus find the solvation of the flexible alkane to be more favorable than that of the rigid alkane. Our findings are consistent with those of Pettitt and co-workers, who showed that the conformation of alkane chains and peptides can influence their hydration free energies substantially [66][67][68]. Our results also lend further support to the notion that surface-area models, which are commonly used to estimate the driving force of hydrophobic assembly, but are incapable of capturing subtle but important differences between the rigid and flexible solutes, are not appropriate for a quantitative treatment of hydrophobic hydration and interactions [66,69].…”

Protein-Solvent Attractive Interactions Dominate the Inverse Temperature Dependence of Polypeptide Hydration Free Energies

“…(ex) p , in this process is 32 ± 128 cal/mol-K -we use the c (ex) p [h(ex) ] values throughout. The uncertainty is necessarily high for reasons noted above, but focusing on the mean value, the trends suggest a positive contribution, just as was found Left panel: The hydration free energy of methane, following(2). With the expected opposition of long-range/attractive interactions to the other contributions, the unfavorable net hydration free energy (filled-pentagons) increases with increasing T , the classic hydrophobic inverse temperature behavior.…”

“…The calculation of µ (ex) and its entropic T s (ex) and enthalpic h (ex) contributions follows earlier work [14][15][16][17][18]. Briefly [8,9,22], the excess chemical potential is given by βµ (ex) = ln e βε , averaging ε over the binding energy distribution P (ε).…”

“…We study the hydration thermodynamics of the decaalanine polypeptide in helical and an extended coil conformation. The coil conformation, labeled C 0 , has the least negative hydration free energy of the coil states studied earlier [16], bounding the free energy of the un-folded ensemble from above [17]. We also study the thermodynamics of a pair of helices in contact.…”

Solvophobic and solvophilic contributions in the water-to-aqueous guanidinium chloride transfer free energy of model peptides

“…8). As already noted, the conditional binding energy distribution is Gaussian to an excellent approximation [5][6][7][8]. The binding energy ε is a sum of van der Waals, ε vdW , and electrostatic, ε elec , contributions.…”