title: Importance of Hydrophilic Hydration and Intramolecular Interactions in the Thermodynamics of Helix-Coil Transition and Helix-Helix Assembly in a Deca-Alanine Peptide.
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.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Johns Hopkins University , Baltimore, Maryland 21218, United States.
authors.forename: Dheeraj S
authors.initials: DS
authors.lastname: Tomar
authors.affiliation: IBM Research, Zurich , CH-8803 Rüschlikon, Switzerland.
authors.forename: Valéry
authors.initials: V
authors.lastname: Weber
authors.affiliation: Sealy Center for Structural Biology and Molecular Biophysics, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch , Galveston, Texas 77555, United States.
authors.forename: B Montgomery
authors.initials: BM
authors.lastname: Pettitt
authors.affiliation: Sealy Center for Structural Biology and Molecular Biophysics, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch , Galveston, Texas 77555, United States.|Department of Chemical and Biomolecular Engineering, Rice University , Houston, Texas 77005, United States.
authors.forename: D
authors.initials: D
authors.lastname: Asthagiri
mesh_terms: D000409:Alanine / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D010455:Peptides; D014867:Water; D000409:Alanine