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.

Sequence-dependent structural properties of B-DNA: what have we learned in 40 years?

The structure of B-DNA, the physiological form of the DNA molecule, has been a central topic in biology, chemistry and physics. Far from uniform and rigid, the double helix was revealed as a flexible and structurally polymorphic molecule. Conformational changes that lead to local and global changes in the helix geometry are mediated by a complex choreography of base and backbone rearrangements affecting the ability of the B-DNA to recognize ligands and consequently on its functionality. In this sense, the knowledge obtained from the sequence-dependent structural properties of B-DNA has always been thought crucial to rationalize how ligands and, most notably, proteins recognize B-DNA and modulate its activity, i.e. the structural basis of gene regulation. Honouring the anniversary of the first high-resolution X-ray structure of a B-DNA molecule, in this contribution, we present the most important discoveries of the last 40 years on the sequence-dependent structural and dynamical properties of B-DNA, from the early beginnings to the current frontiers in the field.