A novel method reveals that solvent water favors polyproline II over β-strand conformation in peptides and unfolded proteins: Conditional hydrophobic accessible surface area (CHASA)

Patrick J. Fleming, Nicholas C. Fitzkee, Mihaly Mezei, Rajgopal Srinivasan, George D. Rose

Research output: Contribution to journalArticlepeer-review

Abstract

In aqueous solution, the ensemble of conformations sampled by peptides and unfolded proteins is largely determined by their interaction with water. It has been a long-standing goal to capture these solute-water energetics accurately and efficiently in calculations. Historically, accessible surface area (ASA) has been used to estimate these energies, but this method breaks down when applied to amphipathic peptides and proteins. Here we introduce a novel method in which hydrophobic ASA is determined after first positioning water oxygens in hydrogen-bonded orientations proximate to all accessible peptide/protein backbone N and O atoms. This conditional hydrophobic accessible surface area is termed CHASA. The CHASA method was validated by predicting the polyproline-II (PII) and β-strand conformational preferences of non-proline residues in the coil library (i.e., non-α-helix, non-β-strand, non-β-turn library derived from X-ray elucidated structures). Further, the method successfully rationalizes the previously unexplained solvation energies in polyalanyl peptides and compares favorably with published experimentally determined PII residue propensities. We dedicate this paper to Frederic M. Richards.

Original languageEnglish (US)
Pages (from-to)111-118
Number of pages8
JournalProtein Science
Volume14
Issue number1
DOIs
StatePublished - Jan 2005

Keywords

  • CHASA
  • Coil library
  • Conditional hydrophobic accessible surface area
  • Polyproline-II
  • Probability density map
  • Solvation energy

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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