Modeling the Sequence Dependent Rigidity of DNA with a Molecular Dynamics Parameterized Rigid Base Model

Abstract

The sequence of nucleotides in a DNA molecule varies its mechanical properties. This provides a mechanism for sequence specificity in the binding of proteins that distort the shape of DNA, such as in the nucleosome. Additionally, the formation of DNA loops, which are used in gene regulation, can be effected by the sequence dependent mechanical properties. To better understand and predict this sequence specificity necessitates an accurate mechanical model of DNA.Previous work in our lab has shown that a rigid base model performs significantly better than a rigid base pair model. We determine all parameters for this coarse grained model from molecular dynamics simulations. Using a direct Monte Carlo sampling method the sequence averaged persistence length of the coarse grained model with these parameters was determined and found to be in excellent agreement with experimental results. To evaluate whether the sequence dependent mechanical properties are accurately captured experimental cyclization data was reproduced.