Capturing Histone Tails Motion using all-atom Replica-Exchange with Solute Tempering (REST2) Simulations

Full-length histone tails play a well characterized role in nucleosome core particles, and, as intrinsically disordered peptides, represent a current challenge for all-atom molecular dynamics simulations. Beyond the choice of the force field, the folding and the subsequent interactions with DNA landscape is complex and calls for a robust computational protocol capable of reproducibility. In this contribution, we assessed by a specifically tailored REST2-based simulation protocol the interaction between the four canonical histone tails and a DNA fragment from a canonical nucleosome core particles. We report contact maps obtained by clus- tering along several microseconds which prefigure plausible interactions between some of the positively-charged residues and DNA. Two major post-translational modifica- tions of lysines are also discussed. Our work thus contributes to pave the way toward a robust in silico predictive tool for DNA-histone tails interactions which remain ex- perimentally difficult to assess although of key importance in Biochemistry.