Peptide bond planarity constrains hydrogen bond geometry and influences secondary structure conformations

An extensive database study of hydrogen bonds in different protein environments showed systematic variations in donor-acceptor-acceptor antecedent angle (ii) and donor-acceptor distance. Protein environments were characterized by depth (distance of amino acids from bulk solvent), secondary structure, and whether the donor/acceptor belongs to the main chain (MC) or side chain (SC) of amino acids. The MC-MC hydrogen bonds (whether in secondary structures or not) have (H) over cap angles tightly restricted to a value of around 155 degrees, which was distinctly different from other (H) over cap angles. Quantum chemical calculations attribute this characteristic MC-MC (H) over cap angle to the nature of the electron density distribution around the planar peptide bond. Additional classical simulations suggest a causal link between MC-MC (H) over cap angle and the conformation of secondary structures in proteins. We also showed that donor-acceptor distances are environment dependent, which has implications on protein stability. Our results redefine hydrogen bond geometries in proteins and suggest useful refinements to existing molecular mechanics force fields.