Peptide bond planarity constrains hydrogen bond geometry and influences secondary structure conformations
Kuan Pern Tan, Khushboo Singh, Anirban Hazra, M. S. Madhusudhan
Abstract
An extensive database study of hydrogen bonds in different protein environments showed systematic variations in donor-acceptor-acceptor antecedent angle (Ĥ) 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 Ĥ angles tightly restricted to a value of around 155°, which was distinctly different from other Ĥ angles. Quantum chemical calculations attribute this characteristic MC-MC Ĥ angle to the nature of the electron density distribution around the planar peptide bond. Additional classical simulations suggest a causal link between MC-MC Ĥ 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.