Hydrogen bond

Protein folding

Amide

Biology

Molecule

Biophysics

Protein structure

Engineering

Folding (DSP implementation)

Biochemistry

Organic chemistry

Crystallography

Chemistry

Electrical engineering

Nature Chemical Biology

Within polypeptides, C5 hydrogen bonds form between the amide proton and carbonyl oxygen of the same residue. This intraresidue interaction stabilizes β-sheets in particular and is widespread throughout structurally characterized proteins.                                                                 Current limitations in de novo protein structure prediction and design suggest an incomplete understanding of the interactions that govern protein folding. Here we demonstrate that previously unappreciated hydrogen bonds occur within proteins between the amide proton and carbonyl oxygen of the same residue. Quantum calculations, infrared spectroscopy, and nuclear magnetic resonance spectroscopy show that these interactions share hallmark features of canonical hydrogen bonds. Biophysical analyses demonstrate that selective attenuation or enhancement of these C5 hydrogen bonds affects the stability of synthetic β-sheets. These interactions are common, affecting approximately 5% of all residues and 94% of proteins...

A prevalent intraresidue hydrogen bond stabilizes proteins