Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Poster Abstracts

18-POS Board 18 MODELLING OF ELASTIN POLYPEPTIDES BY ASSEMBLY OF RIGID BODIES AND SIMULATIONS IN AN EXTRACELLULAR MATRIX VIRTUAL MODEL Camille Depenveiller 1 ; Hua Wong 1 ; Jean-Marc Crowet 1 ; Stéphanie Baud 1 ; Manuel Dauchez 1 ; Nicolas Belloy 1 ; 1 UMR CNRS/URCA 7369 MEDyC / MAgICS, University of Reims Champagne-Ardenne, Reims, France Extracellular matrix (ECM) is a tridimensional network composed of large macromolecules and plays a key role in supporting tissues and organs. Dysfunction of ECM components, due to structure changes or generation of fragments with physiopathological effects, may lead to some diseases. The precise organization of the ECM remains poorly known, since experimental data is rare or difficult to obtain. Classical molecular dynamics simulations are of interest to study domains of ECM proteins, but inappropriate for large multi-domain macromolecules. However, to handle such huge molecules at the mesoscopic scale, a dedicated numerical environment allowing to model and simulate large biological systems as dynamic chains of rigid bodies has been developed. Rigid bodies are modules representing the domains composing each molecule and allow to describe representative conformations of molecules by simple shapes called primitives. The project aims to extend this approach to elastin and its monomer tropoelastin. Thus, classical molecular dynamics are first performed on characteristic peptide motifs of tropoelastin. Then, using different clustering methods allows to sample the conformational space along molecular dynamics trajectories, in order to get the main characteristic conformations of the peptides. Properties such as hydrophobicity and electrostatics are also analyzed. Simulations are then adapted at the mesoscopic scale to rigid bodies. Each polypeptide is built by an assembly of rigid bodies, linked together with molecular joints, on which constraints determined by characteristic angles between motifs are defined. Elastin polypeptides conformations and properties will be integrated in the ECM virtual model. These results will enable to understand the behavior of the proteins and the structure-function-dynamics relationships. These new insights will allow for a better understanding of the elasticity, the structural properties and thus the complexity of the ECM.

93