TY - JOUR

T1 - Intramolecular Interactions Overcome Hydration to Drive the Collapse Transition of Gly15

AU - Asthagiri, D.

AU - Karandur, Deepti

AU - Tomar, Dheeraj S.

AU - Pettitt, B. Montgomery

N1 - Funding Information:
This research used resources of the National Energy Research Scientific Computing Center, which is supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. We gratefully acknowledge the Robert A. Welch Foundation (H-0037) the National Science Foundation (CHE-1152876), and the National Institutesof Health (GM-037657) for partial support of this work. This research also used part of the National Science Foundation XSEDE resources
Publisher Copyright:
© 2017 American Chemical Society.

PY - 2017/8/31

Y1 - 2017/8/31

N2 - 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.

AB - 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.

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U2 - 10.1021/acs.jpcb.7b05469

DO - 10.1021/acs.jpcb.7b05469

M3 - Article

C2 - 28774177

AN - SCOPUS:85028654123

VL - 121

SP - 8078

EP - 8084

JO - Journal of Physical Chemistry B

JF - Journal of Physical Chemistry B

SN - 1089-5647

IS - 34

ER -