A bottom-up coarse-grained model for nucleosome–nucleosome interactions with explicit ions

• Main Authors: Sun, Tiedong, Minhas, Vishal, Mirzoev, Alexander, Korolev, Nikolay, Lyubartsev, Alexander P., Nordenskiöld, Lars
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2022
• Subjects: Science::Biological sciences::Biophysics; Science::Chemistry::Physical chemistry::Thermodynamics; Nucleosome Core Particle; Bottom-Up Coarse-Graining; Divide and Conquer; Inverse Monte Carlo; Cobalt(III)-Hexammine; Explicit Ions
• Online Access: https://hdl.handle.net/10356/161452
• Institution: Nanyang Technological University

The nucleosome core particle (NCP) is a large complex of 145-147 base pairs of DNA and eight histone proteins and is the basic building block of chromatin that forms the chromosomes. Here, we develop a coarse-grained (CG) model of the NCP derived through a systematic bottom-up approach based on underlying all-atom MD simulations to compute the necessary CG interactions. The model produces excellent agreement with known structural features of the NCP and gives a realistic description of the nucleosome-nucleosome attraction in the presence of multivalent cations (Mg(H2O)62+ or Co(NH3)63+) for systems comprising 20 NCPs. The results of the simulations reveal structural details of the NCP-NCP interactions unavailable from experimental approaches, and this model opens the prospect for the rigorous modeling of chromatin fibers.