Importance of Hydrophilic Hydration and Intramolecular Interactions in the Thermodynamics of Helix-Coil Transition and Helix-Helix Assembly in a Deca-Alanine Peptide

Dheeraj S. Tomar, Valéry Weber, B. Montgomery Pettitt, D. Asthagiri

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25 Scopus citations

Abstract

For a model deca-alanine peptide the cavity (ideal hydrophobic) contribution to hydration favors the helix state over extended states and the paired helix bundle in the assembly of two helices. The energetic contributions of attractive protein-solvent interactions are separated into quasi-chemical components consisting of a short-range part arising from interactions with solvent in the first hydration shell and the remaining long-range part that is well described by a Gaussian. In the helix-coil transition, short-range attractive protein-solvent interactions outweigh hydrophobic hydration and favor the extended coil states. Analysis of enthalpic effects shows that it is the favorable hydration of the peptide backbone that favors the unfolded state. Protein intramolecular interactions favor the helix state and are decisive in favoring folding. In the pairing of two helices, the cavity contribution outweighs the short-range attractive protein-water interactions. However, long-range, protein-solvent attractive interactions can either enhance or reverse this trend depending on the mutual orientation of the helices. In helix-helix assembly, change in enthalpy arising from change in attractive protein-solvent interactions favors disassembly. In helix pairing as well, favorable protein intramolecular interactions are found to be as important as hydration effects. Overall, hydrophilic protein-solvent interactions and protein intramolecular interactions are found to play a significant role in the thermodynamics of folding and assembly in the system studied.

Original languageEnglish
Pages (from-to)69-76
Number of pages8
JournalJournal of Physical Chemistry B
Volume120
Issue number1
DOIs
StatePublished - Jan 14 2016
Externally publishedYes

Funding

We thank Lawrence Pratt and Mike Paulaitis for their critical reading of the manuscript and for helpful discussions. We thank Chris Roberts and Bramie Lenhoff for encouraging comments. We thank Gerhard Hummer and Mike Pacella for helpful comments on an early version of the manuscript. D.A. gratefully acknowledges the encouragement provided by Walter Chapman and Ken Cox at Rice University. D.A. and B.M.P. gratefully acknowledge the financial support of the National Institutes of Health (GM 037657), the National Science Foundation (CHE-1152876) and the Robert A. Welch Foundation (H-0037). 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.

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