title: Atomistic Simulation of Stacked Nucleosome Core Particles: Tail Bridging, the H4 Tail, and Effect of Hydrophobic Forces.
abstract: We report the first atomistic simulation of two stacked nucleosome core particles (NCPs), with an aim to understand, in molecular detail, how they interact, the effect of salt concentration, and how different histone tails contribute to their interaction, with a special emphasis on the H4 tail, known to have the largest stabilizing effect on the NCP-NCP interaction. We do not observe specific K16-mediated interaction between the H4 tail and the H2A-H2B acidic patch, in contrast with the findings from crystallographic studies, but find that the stacking was stable even in the absence of this interaction. We perform simulations with the H4 tail (partially/completely) removed and find that the region between LYS-16 and LYS-20 of the H4 tail holds special importance in mediating the inter-NCP interaction. Performing similar tail-clipped simulations with the H3 tail removed, we compare the roles of the H3 and H4 tails in maintaining the stacking. We discuss the relevance of our simulation results to the bilayer and other liquid-crystalline phases exhibited by NCPs in vitro and, through an analysis of the histone-histone interface, identify the interactions that could possibly stabilize the inter-NCP interaction in these columnar mesophases. Through the mechanical disruption of the stacked nucleosome system using steered molecular dynamics, we quantify the strength of inter-NCP stacking in the presence and absence of salt. We disrupt the stacking at some specific sites of internucleosomal tail-DNA contact and perform a comparative quantification of the binding strengths of various tails in stabilizing the stacking. We also examine how hydrophobic interactions may contribute to the overall stability of the stacking and find a marked difference in the role of hydrophobic forces as compared with electrostatic forces in determining the stability of the stacked nucleosome system.
authors.affiliation: Center for Condensed Matter Theory, Department of Physics, Indian Institute of Science , Bangalore, Karnataka 560012, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Saurabh
authors.affiliation: Department of Physics and Liquid Crystal Materials Research Center, University of Colorado , Boulder, Colorado 80309, United States.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Glaser
authors.affiliation: GREMAN, Université François Rabelais, CNRS UMR 7347 , 37200 Tours, France.|School of Materials Science and Engineering, Gwangju Institute of Science and Technology , Gwangju 61005, Korea.
authors.forename: Yves
authors.initials: Y
authors.lastname: Lansac
authors.affiliation: Center for Condensed Matter Theory, Department of Physics, Indian Institute of Science , Bangalore, Karnataka 560012, India.
authors.forename: Prabal K
authors.initials: PK
authors.lastname: Maiti
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D009707:Nucleosomes / Q000737:chemistry*; D010316:Particle Size
chemical_list: D009707:Nucleosomes