Analyses of displacements resulting from a point mutation in proteins
Résumé
The effects of a single residue substitution on the protein backbone are frequently quite small but there are many other potential sources of structural variation for protein. We present here a methodology considering different sources of distortions in order to isolate the very effect of the mutation. To validate our methodology, we consider a well-studied family with many single mutants: the human lysozyme. Most of the perturbations are expected to be at the very localisation of the mutation, but in many cases the effects are propagated at long range. We show that the distances between the mutated residue and the 5% most disturbed residues, exponentially decreases. One third of the affected residues are in direct contact with the mutated position; the remaining two thirds are potential allosteric effects. We confirm the reliability of the residues assigned as significantly perturbed by comparing our results to experimental studies. We confirm with the present method all the previously identified perturbations. This study shows that mutations have long-range impact on protein backbone that can be detected, although the displacement of the affected atoms is small.
Fichier principal
Analysis of displacements-JSB-revised-Unmarked.pdf (278.96 Ko)
Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...