title: Redrawing the Ramachandran plot after inclusion of hydrogen-bonding constraints.
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.
authors.affiliation: T. C. Jenkins Department of Biophysics, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
authors.forename: Lauren L
authors.initials: LL
authors.lastname: Porter
authors.forename: George D
authors.initials: GD
authors.lastname: Rose
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000378:metabolism; D030562:Databases, Protein; D006860:Hydrogen Bonding; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D000577:Amides