Geometrical constraints and system dynamics : the case of the transthyretin fiber formation

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.

Biological fiber formation, Geometrical transition from oligomer to fiber, Tiling theory and group theory, Amino acid contact network, Topological invariant in graphs

Partenaires du projet

Vuillon Laurent
LAMA (UMR5127) Le Bourget du Lac France
Lesieur Claire
AMPERE (UMR5005) Le Bourget du Lac France
Rivalta Ivan
Laboratoire de Chimie (UMR 5819) France
Crédit photo : Laurent VUILLON