TY - JOUR
T1 - Redrawing the Ramachandran plot after inclusion of hydrogen-bonding constraints
AU - Porter, Lauren L.
AU - Rose, George D.
PY - 2011/1/4
Y1 - 2011/1/4
N2 - 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.
AB - 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.
KW - Helix nucleation
KW - Hydrogen bonding
KW - Protein folding
KW - β-turns
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U2 - 10.1073/pnas.1014674107
DO - 10.1073/pnas.1014674107
M3 - Article
C2 - 21148101
AN - SCOPUS:78651105014
SN - 0027-8424
VL - 108
SP - 109
EP - 113
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 1
ER -