Intramolecular Interactions Overcome Hydration to Drive the Collapse Transition of Gly 15

• Published in: The journal of physical chemistry. B 2017-08, Vol.121 (34), p.8078-8084
• Main Authors: Asthagiri, D, Karandur, Deepti, Tomar, Dheeraj S, Pettitt, B Montgomery
• Format: Article
• Language: English
• Subjects: Algorithms; Glycine - chemistry; Hydrophobic and Hydrophilic Interactions; Peptides - chemistry; Peptides - metabolism; Thermodynamics; Water - chemistry
• ISSN: 1520-6106; 1520-5207
• DOI: 10.1021/acs.jpcb.7b05469

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(R |r), of the radius of gyration for a given value of r. The free energy change versus R , -k T ln P(R |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.