Significance of Knotted Structures for Function of Proteins and Nucleic Acids - September 17-21, 2014

Significance of Knotted Structures for Function of Proteins and Nucleic Acids

Poster Session I

11 – POS Board 11 Mapping Consitutive Law of Biological Filaments from MD Simulations Sachin Goyal . University of California, Merced, USA.

Dynamics of bending and twisting deformations of biological filaments such as DNA play a central role in their biological functions. For example, looping of DNA is an important step in gene regulatory mechanisms, which is often mediated by protein binding. Continuum models such as elastic rod have evolved as efficient computational tools to simulate the nonlinear dynamics of large twisting and bending of biological filaments. However, a major roadblock to this approach is the inaccurate modeling of the constitutive law, which captures the restoring effects in the bending and torsional deformations of the filament in question and which depends on the filament’s atomistic-level structure. Traditional models assume a linear constitutive law and experimental measurements focus on the estimation of just a handful of stiffness parameters such as bending and torsional stiffness. Only recently the focus has shifted to examining the dependence of the stiffness parameters on the base-pair sequence. We are developing a methodology to map non-linear constitutive laws directly from molecular dynamics (MD) simulations without any a priori assumptions of its functional form. The methodology employs a two-step technique using an inverse rod model. Step one estimates the curvature and twist along with internal restoring moments and forces at every cross-section in the deformed states of the filament obtained from MD simulations. Step two fits a constitutive law through the estimated data using function-fitting. We have validated the approach with proof-of-concept results, and have also analyzed its robustness by adding noise in the data.

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