Multiscale modelling of nucleosome core particle aggregation

The nucleosome core particle (NCP) is the basic building block of chromatin. Under the influence of multivalent cations, isolated mononucleosomes exhibit a rich phase behaviour forming various columnar phases with characteristic NCP–NCP stacking. NCP stacking is also a regular element of chromatin s...

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Main Authors: Fan, Yanping, Nordenskiöld, Lars, Lyubartsev, Alexander P, Korolev, Nikolay
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2016
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Online Access:https://hdl.handle.net/10356/82785
http://hdl.handle.net/10220/40277
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-827852023-02-28T16:56:33Z Multiscale modelling of nucleosome core particle aggregation Fan, Yanping Nordenskiöld, Lars Lyubartsev, Alexander P Korolev, Nikolay School of Biological Sciences Nucleosome core particles Chromatin compaction Multivalent ions Coarse-grained models Multiscale simulations Inverse Monte Carlo The nucleosome core particle (NCP) is the basic building block of chromatin. Under the influence of multivalent cations, isolated mononucleosomes exhibit a rich phase behaviour forming various columnar phases with characteristic NCP–NCP stacking. NCP stacking is also a regular element of chromatin structure in vivo. Understanding the mechanism of nucleosome stacking and the conditions leading to self-assembly of NCPs is still incomplete. Due to the complexity of the system and the need to describe electrostatics properly by including the explicit mobile ions, novel modelling approaches based on coarse-grained (CG) methods at the multiscale level becomes a necessity. In this work we present a multiscale CG computer simulation approach to modelling interactions and self-assembly of solutions of NCPs induced by the presence of multivalent cations. Starting from continuum simulations including explicit three-valent cobalt(III)hexammine (CoHex3+) counterions and 20 NCPs, based on a previously developed advanced CG NCP model with one bead per amino acid and five beads per two DNA base pair unit (Fan et al 2013 PLoS One 8 e54228), we use the inverse Monte Carlo method to calculate effective interaction potentials for a 'super-CG' NCP model consisting of seven beads for each NCP. These interaction potentials are used in large-scale simulations of up to 5000 NCPs, modelling self-assembly induced by CoHex3+. The systems of 'super-CG' NCPs form a single large cluster of stacked NCPs without long-range order in agreement with experimental data for NCPs precipitated by the three-valent polyamine, spermidine3+. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2016-03-15T04:34:06Z 2019-12-06T15:05:31Z 2016-03-15T04:34:06Z 2019-12-06T15:05:31Z 2015 Journal Article Lyubartsev, A. P., Korolev, N., Fan, Y., & Nordenskiöld, L. (2015). Multiscale modelling of nucleosome core particle aggregation. Journal of Physics: Condensed Matter, 27(6), 064111-. 0953-8984 https://hdl.handle.net/10356/82785 http://hdl.handle.net/10220/40277 10.1088/0953-8984/27/6/064111 en Journal of Physics: Condensed Matter © 2015 IOP Publishing Ltd. Content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI. 11 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Nucleosome core particles
Chromatin compaction
Multivalent ions
Coarse-grained models
Multiscale simulations
Inverse Monte Carlo
spellingShingle Nucleosome core particles
Chromatin compaction
Multivalent ions
Coarse-grained models
Multiscale simulations
Inverse Monte Carlo
Fan, Yanping
Nordenskiöld, Lars
Lyubartsev, Alexander P
Korolev, Nikolay
Multiscale modelling of nucleosome core particle aggregation
description The nucleosome core particle (NCP) is the basic building block of chromatin. Under the influence of multivalent cations, isolated mononucleosomes exhibit a rich phase behaviour forming various columnar phases with characteristic NCP–NCP stacking. NCP stacking is also a regular element of chromatin structure in vivo. Understanding the mechanism of nucleosome stacking and the conditions leading to self-assembly of NCPs is still incomplete. Due to the complexity of the system and the need to describe electrostatics properly by including the explicit mobile ions, novel modelling approaches based on coarse-grained (CG) methods at the multiscale level becomes a necessity. In this work we present a multiscale CG computer simulation approach to modelling interactions and self-assembly of solutions of NCPs induced by the presence of multivalent cations. Starting from continuum simulations including explicit three-valent cobalt(III)hexammine (CoHex3+) counterions and 20 NCPs, based on a previously developed advanced CG NCP model with one bead per amino acid and five beads per two DNA base pair unit (Fan et al 2013 PLoS One 8 e54228), we use the inverse Monte Carlo method to calculate effective interaction potentials for a 'super-CG' NCP model consisting of seven beads for each NCP. These interaction potentials are used in large-scale simulations of up to 5000 NCPs, modelling self-assembly induced by CoHex3+. The systems of 'super-CG' NCPs form a single large cluster of stacked NCPs without long-range order in agreement with experimental data for NCPs precipitated by the three-valent polyamine, spermidine3+.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Fan, Yanping
Nordenskiöld, Lars
Lyubartsev, Alexander P
Korolev, Nikolay
format Article
author Fan, Yanping
Nordenskiöld, Lars
Lyubartsev, Alexander P
Korolev, Nikolay
author_sort Fan, Yanping
title Multiscale modelling of nucleosome core particle aggregation
title_short Multiscale modelling of nucleosome core particle aggregation
title_full Multiscale modelling of nucleosome core particle aggregation
title_fullStr Multiscale modelling of nucleosome core particle aggregation
title_full_unstemmed Multiscale modelling of nucleosome core particle aggregation
title_sort multiscale modelling of nucleosome core particle aggregation
publishDate 2016
url https://hdl.handle.net/10356/82785
http://hdl.handle.net/10220/40277
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