Available online 19 October 2022, 107907

Rigorous investigation of distributions of polypeptide backbone dihedral angles

Methods based on recently-developed statistical techniques

The influence of right and left neighbors cannot be considered independently

Three-residue fragments should be considered as the minimal building blocks

Backbone dihedral angles ϕ and ψ are the main structural descriptors of proteins and peptides. The distribution of these angles has been investigated over decades as they are essential for the validation and refinement of experimental measurements, as well as for structure prediction and design methods. The dependence of these distributions, not only on the nature of each amino acid but also on that of the closest neighbors, has been the subject of numerous studies. Although neighbor-dependent distributions are nowadays generally accepted as a good model, there is still some controversy about the combined effects of left and right neighbors. We have investigated this question using rigorous methods based on recently-developed statistical techniques. Our results unambiguously demonstrate that the influence of left and right neighbors cannot be considered independently. Consequently, three-residue fragments should be considered as the minimal building blocks to investigate polypeptide sequence-structure relationships.

Protein and peptide structure

Local conformational preferences

Sequence-structure relationship

Statistical tests

Wasserstein distance

© 2022 Elsevier Inc. All rights reserved.