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

• Published in: Current research in structural biology Vol. 3; pp. 1 - 8
• Main Authors: Tan, Kuan Pern, Singh, Khushboo, Hazra, Anirban, Madhusudhan, M.S.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.01.2021; Elsevier
• ISSN: 2665-928X; 2665-928X
• DOI: 10.1016/j.crstbi.2020.11.002

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. [Display omitted] •Hydrogen bonds are known to stabilize the structures of proteins.•We investigated the hydrogen bond types involving the main and side chains of amino acids and their environments.•The different types have unique preferences for donor-acceptor distances as well as for the donor-acceptor-acceptor antecedent (Ĥ) angles.•Classical and quantum calculations implicate the electronic structure of the peptide bond as the origin of these differences.•This study explains the origin of secondary structures and is important for protein characterization and design.