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

Résumé

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.

Mots clés

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

Laurent VUILLON
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