Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Thursday Speaker Abstracts

HYBRID SIMULATIONS OF COLLAGEN FAILURE Benedikt Rennekamp 1,2 ; Frauke Gräter 1,2 ; 1 Heidelberg Institute for Theoretical Studies (HITS), Molecular Biomechanics, Heidelberg, Germany 2 Heidelberg University, Interdisciplinary Center for Scientific Computing, Heidelberg, Germany Structural proteins such as collagen and many other force-bearing biological materials have important functions such as carrying load and providing stability, but also in signaling. For example, we recently found that excessive mechanical load can lead to covalent bond scissions and the creation of mechanoradicals inside collagen fibrils. The implications for the hierarchical structure and subsequent biochemical reactions therein are yet to be determined on the molecular scale. We therefore developed a hybrid Kinetic Monte Carlo / Molecular Dynamics (KIMMDY) simulation scheme featuring bond ruptures that allows to investigate this link between mechanical stress, breakages, and the subsequent dynamical response. Here, bond rupture rates are calculated in the spirit of a transition state model based on the interatomic distances in the MD simulation and then serve as an input for a Kinetic Monte Carlo step. This hybrid approach bridges various time scales between MD and the rupture processes in such complex hierarchical materials, which are - even at the Dawn of Exascale Computers - otherwise not reachable. With this new technique, we investigated bond ruptures in a multi-million atom system of tensed collagen. Our simulations show a clear concentration of homolytic bond scissions near chemical crosslinks in collagen. Having a higher rupture propensity on this molecule side, crosslinks located there can act as a mechanical buffer by releasing additional length of the stressed strands. These breakage sites are located in the vicinity of redox-active amino acids, thereby also acting as a chemical buffer for the arising oxidative stress.

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