Affiliation:
1. AMPERE, CNRS, Université de Lyon, 69622 Lyon, France
2. Institut Rhônalpin des Systèmes Complexes (IXXI), École Normale Supérieure de Lyon, 69007 Lyon, France
Abstract
Abstract
Motivation
The objective is to diagnose dynamics perturbations caused by amino-acid mutations as prerequisite to assess protein functional health or drug failure, simply using network models of protein X-ray structures.
Results
We find that the differences in the allocation of the atomic interactions of each amino acid to 1D, 2D, 3D, 4D structural levels between variants structurally robust, recover experimental dynamic perturbations. The allocation measure validated on two B-pentamers variants of AB5 toxins having 17 mutations, also distinguishes dynamic perturbations of pathogenic and non-pathogenic Transthyretin single-mutants. Finally, the main proteases of the coronaviruses SARS-CoV and SARS-CoV-2 exhibit changes in the allocation measure, raising the possibility of drug failure despite the main proteases structural similarity.
Availability and implementation
The Python code used for the production of the results is available at github.com/lorpac/protein_partitioning_atomic_contacts. The authors will run the analysis on any PDB structures of protein variants upon request.
Supplementary information
Supplementary data are available at Bioinformatics online.
Publisher
Oxford University Press (OUP)
Subject
Computational Mathematics,Computational Theory and Mathematics,Computer Science Applications,Molecular Biology,Biochemistry,Statistics and Probability