Redrawing the Ramachandran plot after inclusion of hydrogen-bonding constraints

Lauren L. Porter, George D. Rose

Research output: Contribution to journalArticlepeer-review

Abstract

A protein backbone has two degrees of conformational freedom per residue, described by its φ,ψ-angles. Accordingly, the energy landscape of a blocked peptide unit can be mapped in two dimensions, as shown by Ramachandran, Sasisekharan, and Ramakrishnan almost half a century ago. With atoms approximated as hard spheres, the eponymous Ramachandran plot demonstrated that steric clashes alone eliminate 3/4 of φ,ψ-space, a result that has guided all subsequent work. Here, we show that adding hydrogen-bonding constraints to these steric criteria eliminates another substantial region of φ,ψ-space for a blocked peptide; for conformers within this region, an amide hydrogen is solvent-inaccessible, depriving it of a hydrogen-bonding partner. Yet, this "forbidden" region is well populated in folded proteins, which can provide longer-range intramolecular hydrogen-bond partners for these otherwise unsatisfied polar groups. Consequently, conformational space expands under folding conditions, a paradigm-shifting realization that prompts an experimentally verifiable conjecture about likely folding pathways.

Original languageEnglish (US)
Pages (from-to)109-113
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number1
DOIs
StatePublished - Jan 4 2011

Keywords

  • Helix nucleation
  • Hydrogen bonding
  • Protein folding
  • β-turns

ASJC Scopus subject areas

  • General

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