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Fundamental processes of protein folding: Measuring the energetic balance between helix formation and hydrophobic interactions
Author(s) -
Xian Wujing,
Connolly Peter J.,
Oslin Marcela,
Hausrath Andrew C.,
Osterhout John J.
Publication year - 2006
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.062297006
Subject(s) - folding (dsp implementation) , protein folding , contact order , chemistry , hydrogen bond , protein secondary structure , helix (gastropod) , downhill folding , hydrophobic effect , lattice protein , crystallography , phi value analysis , protein tertiary structure , chemical physics , native state , molecule , biology , biochemistry , organic chemistry , ecology , snail , electrical engineering , engineering
Abstract Theories of protein folding often consider contributions from three fundamental elements: loops, hydrophobic interactions, and secondary structures. The pathway of protein folding, the rate of folding, and the final folded structure should be predictable if the energetic contributions to folding of these fundamental factors were properly understood. αtα is a helix‐turn‐helix peptide that was developed by de novo design to provide a model system for the study of these important elements of protein folding. Hydrogen exchange experiments were performed on selectively 15 N‐labeled αtα and used to calculate the stability of hydrogen bonds within the peptide. The resulting pattern of hydrogen bond stability was analyzed using a version of Lifson‐Roig model that was extended to include a statistical parameter for tertiary interactions. This parameter, x, represents the additional statistical weight conferred upon a helical state by a tertiary contact. The hydrogen exchange data is most closely fit by the XHC model with an x parameter of 9.25. Thus the statistical weight of a hydrophobic tertiary contact is ∼5.8× the statistical weight for helix formation by alanine. The value for the x parameter derived from this study should provide a basis for the understanding of the relationship between hydrophobic cluster formation and secondary structure formation during the early stages of protein folding.