(723e) Understanding Molecular Machinery of Life: A Study of Histone Protein Dynamics

The folding of human DNA from a single two-meter strand to the chromosome structure found within an approximate ~10 µm cell nucleus is one of biology’s most elegant and elusive packing mechanisms. Beyond the final compact structure, there exists a series of epigenetic mechanisms that govern local and reversible compaction of chromatin without altering genetic sequence. These mechanisms, which are covalent modifications of DNA or the histone proteins associated to the DNA proteins, fine tune the rules of life and are hallmarks of many diseases including cancer. Both experimental and computational studies have pointed to the importance of various chemical modifications to the seemingly unstructured “histone tails.” However, little is known about how these modifications affect overall structure and dynamics of histone proteins and their ability to interact with essential enzymes. This work is a comprehensive all-atomistic molecular dynamics (MD) study of particularly the length and sequence histone H3 tail. Using MD simulations of the whole nucleosome, analysis of changes in the histone structure as well as protein–DNA interaction were investigated. Our results show the biophysical relevance of both the length and sequence of histone H3 tails. Implications of our work could shed the light on how small molecular changes impact large biological processes like chromatin compaction.