Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Poster Abstracts

33-POS Board 33 DEVELOPMENT OF DNA FORCE FIELDS AND THE IMPACT OF TOPOLOGICAL STRESS ON REGULATORY SITES AND DNA DAMAGES Korbinian Liebl 1,2 ; Martin Zacharias 2 ; The quality of force fields is central to the accuracy of Molecular Dynamics (MD) simulations. However, many of the modern DNA force fields still rely on non-bonded parameters derived more than 20 years ago. In this talk, I explain how this motivated me to develop an entirely new DNA force field ('Tumuc1') based on quantum-mechanical calculations. I discuss the development of Tumuc1, show problems and strategies in force field parameterization and analyze the performance of Tumuc1. Advanced sampling techniques allowed me to compute base-pair stacking energies. Here, the comparison to experimental data reveals systematic overstabilization of the current force fields. Thus, I also present recent attempts to fix this deficiency and outline the route to a force field which captures DNA's stability accurately. In a next step, I share unpublished data of MD simulations of ~200 base-pair long, circularly closed DNA molecules exposed to explicit solvent. These simulations were performed on the NHR supercomputer in Erlangen, hence facilitating sufficient sampling, and give valuable insight into how topological stress exposes regulatory DNA sequences and UV damages. This topic is of outmost biological relevance, as DNA is constantly under topological stress in vivo, and I point out how this affects base-pair flipping and local melting, for instance. 1 Technical University, Chemistry, Munich, Germany 2 Technical University, Physics, Munich, Germany

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