The project investigates the relationships between the geometrical constraints and the dynamics of a system. The case study is the transition, induced by an amino acid mutation, of a protein oligomer to a protein fiber, transition, associated with many diseases (e.g. Alzheimer, type II diabetes, Parkinson, etc.)1. To model the fiber, the project is divided in three steps, each associated with a scale relevant to the problem. First, the amino acids and interactions affected by the mutation are identified using a network at the local scale of amino acids. These resides constitute the new interface required for the fiber. Second, the interactions between proteins within the interface domain in the fiber are modeled using a network at the scale of the interface. Finally, the last scale is the fiber whose construction is modeled using a tiling model. The combination of both network and tiling models allows reconciling all experimental data on fiber formation because tiling takes into account a scale uncovers by networks.
GeoFiber Geometrical constraints and system dynamics : the case of the transthyretin fiber formation
Résumé
Mots clés
- Amino acid contact networkBiological fiber formationGeometrical transition from oligomer to fiberTiling theory and group theoryTopological invariant in graphs
Partenaires du projet
INSMI
Laurent Vuillon
LAMA
(UMR5127) Le Bourget du Lac, France
INSIS
Claire Lesieur
AMPERE
(UMR5005) Le Bourget du Lac, France
INC
Ivan Rivalta
Laboratoire de Chimie
(UMR 5819) France