Predicting the Configuration and Energy of DNA in a Nucleosome by Coarse-Grain Modelling

Nucleosome-binding propensities of DNA are crucial for understanding gene expression and regulation. Therefore, it is important to understand how specific DNA sequences self-organise and optimise the process of wrapping into the nucleosomes. To this end, we develop a procedure to predict the configuration needed for nucleosome forming. We start with examining a set of chosen experimental structures of nucleosomes to find regularities. This classification allows us to define structural constraints for DNA wound around histones. We then use the cgDNA+ model, which is a coarse-grained model of DNA bases and phosphates, to compute the free energy of a given DNA configuration for a given sequence. Minimising the free energy subject to the aforementioned structural constraints results in a preferred configuration for a given DNA sequence on a nucleosome. The energetic cost of forming a nucleosome with a particular DNA sequence can then be computed. We use this framework to compare the energetic costs with the persistence length of the same DNA sequence to verify whether less rigid (lower persistence length) sequences require less energy to wrap into nucleosomes.