ИСТИНА

Recent decades have witnessed tremendous progress in DNA sequencing and availability of complete genomic sequences for many living organisms. The digital-like discrete encoding of the genetic information within the primary se-quence of the DNA opened many possibilities for bioinformatic analysis. Howev-er, understanding the functioning of the genomes ultimately requires the under-standing of the 3D structural interactions between the DNA/RNA, proteins and their dynamics. In eukaryotic organisms, chromatin – the complex of DNA, RNA, histone and non-histone proteins – provides a complex framework for genome functioning and regulation. Deciphering the mechanisms of eukaryotic chromatin operation starts with understanding the structure and dynamics of the nucleo-somes – the basic units of chromatin. Nucleosomes comprise an octamer of eight histone proteins and around 150 DNA base pairs wrapped around it. The canoni-cal structure of the nucleosome was revealed by X-ray crystallography 25 years ago. It has since become apparent that at physiological conditions nucleosomes are highly dynamic and this dynamics is instrumental for genome functioning at epi-genetic level [1]. However, despite recent progress in structural biology techniques we are still facing conceptual and methodological challenges in describing and un-derstanding how large dynamic macromolecular such as nucleosomes function. In this report I will showcase how combination of atomistic and coarse-grained supercomputer simulations supplemented with data from various biophys-ical and biochemical experiments can be used to study the structure and dynamics of chromatin at nucleosome and supranucleosome levels. Based on our works I will first discuss data analysis and modeling approaches that may be used to re-construct the structures of arbitrary nucleosomes based on hydroxyl-radical foot-printing experiments [2,3]. In such experiments the DNA is cleaved within the nucleosome at solvent-accessible sites. Modeling of this process combined with pseudosymmetry of the nucleosome core allows for the reconstruction of the ex-act rotational and translational positioning of the DNA in nucleosomes. I will next discuss the application of atomistic supercomputer molecular dynamics (MD) simulations to decipher the functional motions of histones and DNA in nucleo-somes [4]. Record long MD simulations at a timescale exceeding 10 microseconds allowed us to analyze the interplay between histone and DNA dynamics that facili-tates nucleosome sliding along the DNA and regulates access of transcription ma-chinery to the genetic information. I will conclude with showing how coarse-grained modeling and integrative modeling approaches may be used to model the structure of nucleosome complexes with chromatin proteins and the structure of chromatin fibrils.