Building DNA Coarse-Grain Potentials for the Modeling of DNA-Peptide Complexes

Specific interactions between proteins and DNA are fundamental to many biological processes. Specifically, the ability of proteins to recognize specific DNA sequences is a hallmark of biological regulatory processes. The recognition of specific DNA sequences by proteins is thought to depend on two types of mechanism: one that involves the formation of hydrogen bonds with specific bases, primarily in the major groove, and one involving sequence-dependent deformations of the DNA helix. Focusing on the latter of these two mechanisms, we present two different approaches to building a DNA coarse-grained model that incorporates sequence dependence in the description of the potential interactions. We then compare their ability to describe DNA-peptide interactions by measuring various properties such as minor-groove width, deformability, bending free energy and histone binding. The results from this work provide a list of the most important physical aspects of DNA that need to be included in a mesoscopic model in order to properly, and efficiently describe DNA-peptide interactions and predict mechanisms of recognition.