Biophysical Society Thematic Meeting| Les Houches 2019

Multiscale Modeling of Chromatin: Bridging Experiment with Theory

Poster Abstracts

22-POS Board 22 MONONUCLEOSOME UNDER TENSION Govardhan Reddy Patluri 1 ; Devarajan Thirumalai 2 ; 1 Indian Institute of Science, , Bangalor, Karnataka, 2 India University of Texas at Austin, , Austin, Texas, United States Nucleosome plays an important role in the intricate packing and arrangement of chromatin in the cell nucleus. The effect of external force on the DNA in a mononucleosome is studied using Brownian dynamics simulations and a coarse grained model of the nucleosome. The simulations in agreement with the experiments shows that DNA unravels from the histone protein core (HPC) in two major steps. The simulations show that in the first step, the outer turn of the DNA (1.6 turns to 1.0 turn of DNA) unravels from the HPC and is independent of the pulling direction indicating that the energy barrier in the transition is due to overcoming the DNA-Histone protein contacts. In the second step, which is the unfolding of the inner turn of the DNA (from 1.0 turn to less than 0.5 turns of DNA) from HPC depends on the strength of the interaction of the histone tails with the DNA and pulling direction indicating that kinetic barriers play a role in this transition. In the unfolding transition, the kinetic barriers arise due to the requirement of generating sufficient torque by the external force to rotate the HPC by 180o and the histone tails which interact with the DNA, prevents the HPC from rotating. The refolding of the DNA onto HPC in the second transition upon force quench occurs only when the principal moment of inertia of the HPC aligns along the pulling direction due to stochastic fluctuations, and the external force does not play any role in this alignment. This difference in the role played by the external force in the DNA folding and unfolding from the HPC can contribute to the hysteresis observed in the nucleosome force pulling experiments

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