RT Journal Article
SR Electronic
T1 Defining amino acid pairs as structural units suggests mutation sensitivity to adjacent residues
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.10.23.513383
DO 10.1101/2022.10.23.513383
A1 Aviv A. Rosenberg
A1 Nitsan Yehishalom
A1 Ailie Marx
A1 Alex Bronstein
YR 2022
UL http://biorxiv.org/content/early/2022/10/23/2022.10.23.513383.abstract
AB Proteins fold from chains of amino acids, forming secondary structures, α-helices and β-strands, that, at least for globular proteins, subsequently fold into a three-dimensional structure. A large-scale analysis of high-resolution protein structures suggests that amino acid pairs constitute another layer of ordered structure, more local than these conventionally defined secondary structures. We develop a cross-peptide-bond Ramachandran plot that captures the conformational preferences of the amino acid pairs and show that the effect of a particular mutation on the stability of a protein depends in a predictable manner on the adjacent amino acid context.One-Sentence Summary Large-scale protein backbone analysis reveals amino acid pair conformational preferences and predicts how sequence context affects mutant stability.Competing Interest StatementThe authors have declared no competing interest.