Extracting collective motions underlying nucleosome dynamics via nonlinear manifold learning

Guo, Ashley Z.; Lequieu, Joshua; de Pablo, Juan J.

doi:10.1063/1.5063851

Title: Extracting collective motions underlying nucleosome dynamics via nonlinear manifold learning

Abstract

The identification of effective collective variables remains a challenge in molecular simulations of complex systems. Here, we use a nonlinear manifold learning technique known as the diffusion map to extract key dynamical motions from a complex biomolecular system known as the nucleosome: a DNA-protein complex consisting of a DNA segment wrapped around a disc-shaped group of eight histone proteins. We show that without any a priori information, diffusion maps can identify and extract meaningful collective variables that characterize the motion of the nucleosome complex. We find excellent agreement between the collective variables identified by the diffusion map and those obtained manually using a free energy-based analysis. Notably, diffusion maps are shown to also identify subtle features of nucleosome dynamics that did not appear in those manually specified collective variables. For example, diffusion maps identify the importance of looped conformations in which DNA bulges away from the histone complex that are important for the motion of DNA around the nucleosome. As a result, this work demonstrates that diffusion maps can be a promising tool for analyzing very large molecular systems and for identifying their characteristic slow modes.

Authors:

^[1];

^[1]; de Pablo, Juan J. ^[2]

Univ. of Chicago, Chicago, IL (United States)
Univ. of Chicago, Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)

Publication Date:: Mon Feb 04 00:00:00 EST 2019

Research Org.:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Org.:: Univ. of Chicago, Research Computing Center; National Science Foundation (NSF); USDOE

OSTI Identifier:: 1558001

Grant/Contract Number:: AC02-06CH11357

Resource Type:: Accepted Manuscript

Journal Name:: Journal of Chemical Physics

Additional Journal Information:: Journal Volume: 150; Journal Issue: 5; Journal ID: ISSN 0021-9606

Publisher:: American Institute of Physics (AIP)

Country of Publication:: United States

Language:: English

Subject:: 36 MATERIALS SCIENCE

Citation Formats


                    Guo, Ashley Z., Lequieu, Joshua, and de Pablo, Juan J. Extracting collective motions underlying nucleosome dynamics via nonlinear manifold learning.  United States: N. p., 2019. 
Web.  doi:10.1063/1.5063851.

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                    Guo, Ashley Z., Lequieu, Joshua, & de Pablo, Juan J. Extracting collective motions underlying nucleosome dynamics via nonlinear manifold learning.  United States.  https://doi.org/10.1063/1.5063851

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                    Guo, Ashley Z., Lequieu, Joshua, and de Pablo, Juan J. Mon .  
"Extracting collective motions underlying nucleosome dynamics via nonlinear manifold learning".  United States.  https://doi.org/10.1063/1.5063851.  https://www.osti.gov/servlets/purl/1558001.

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@article{osti_1558001,

  title        = {Extracting collective motions underlying nucleosome dynamics via nonlinear manifold learning},

  author       = {Guo, Ashley Z. and Lequieu, Joshua and de Pablo, Juan J.},

  abstractNote = {The identification of effective collective variables remains a challenge in molecular simulations of complex systems. Here, we use a nonlinear manifold learning technique known as the diffusion map to extract key dynamical motions from a complex biomolecular system known as the nucleosome: a DNA-protein complex consisting of a DNA segment wrapped around a disc-shaped group of eight histone proteins. We show that without any a priori information, diffusion maps can identify and extract meaningful collective variables that characterize the motion of the nucleosome complex. We find excellent agreement between the collective variables identified by the diffusion map and those obtained manually using a free energy-based analysis. Notably, diffusion maps are shown to also identify subtle features of nucleosome dynamics that did not appear in those manually specified collective variables. For example, diffusion maps identify the importance of looped conformations in which DNA bulges away from the histone complex that are important for the motion of DNA around the nucleosome. As a result, this work demonstrates that diffusion maps can be a promising tool for analyzing very large molecular systems and for identifying their characteristic slow modes.},

  doi          = {10.1063/1.5063851},

  journal      = {Journal of Chemical Physics},

  number       = 5,

  volume       = 150,

  place        = {United States},

  year         = {Mon Feb 04 00:00:00 EST 2019},

  month        = {Mon Feb 04 00:00:00 EST 2019}

}

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Title: Extracting collective motions underlying nucleosome dynamics via nonlinear manifold learning

Abstract

Citation Formats

Intrinsic map dynamics exploration for uncharted effective free-energy landscapes journal, June 2017

Structure and dynamics of DNA loops on nucleosomes studied with atomistic, microsecond-scale molecular dynamics journal, April 2016

Blocking Transcription Through a Nucleosome with Synthetic DNA Ligands journal, August 2002

In silico evidence for sequence-dependent nucleosome sliding journal, October 2017

Determination of reaction coordinates via locally scaled diffusion map journal, March 2011

Human diseases with underlying defects in chromatin structure and modification journal, October 2001

Dynamics of Nucleosome Invasion by DNA Binding Proteins journal, August 2011

A genomic code for nucleosome positioning journal, July 2006

Evaluation of Dimensionality-Reduction Methods from Peptide Folding–Unfolding Simulations journal, April 2013

Chromatin remodeling by DNA bending, not twisting journal, January 2005

A Global Geometric Framework for Nonlinear Dimensionality Reduction journal, December 2000

Mesoscale Simulation and Machine Learning of Asphaltene Aggregation Phase Behavior and Molecular Assembly Landscapes journal, April 2017

Covalent modifications of histones during development and disease pathogenesis journal, November 2007

Simplifying the representation of complex free-energy landscapes using sketch-map journal, July 2011

Diffusion maps journal, July 2006

Principal Component Analysis book, January 1986

An experimentally-informed coarse-grained 3-site-per-nucleotide model of DNA: Structure, thermodynamics, and dynamics of hybridization journal, October 2013

Artificial nucleosome positioning sequences. journal, October 1989

Frustration, specific sequence dependence, and nonlinearity in large-amplitude fluctuations of allosteric proteins journal, February 2011

Rapid Exploration of Configuration Space with Diffusion-Map-Directed Molecular Dynamics journal, July 2013

Nonlinear Machine Learning of Patchy Colloid Self-Assembly Pathways and Mechanisms journal, April 2014

The structure of DNA in the nucleosome core journal, May 2003

A Mesoscale Model of DNA and Its Renaturation journal, March 2009

Polymer Reptation and Nucleosome Repositioning journal, May 2001

Geometric diffusions as a tool for harmonic analysis and structure definition of data: Multiscale methods journal, May 2005

Systematic characterization of protein folding pathways using diffusion maps: Application to Trp-cage miniprotein journal, February 2015

The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats journal, November 1989

Nonlinear Dimensionality Reduction by Locally Linear Embedding journal, December 2000

Rapid spontaneous accessibility of nucleosomal DNA journal, December 2004

SSAGES: Software Suite for Advanced General Ensemble Simulations journal, January 2018

Crystal structure of the nucleosome core particle at 2.8 Å resolution journal, September 1997

Crystal Structures of Nucleosome Core Particles in Complex with Minor Groove DNA-binding Ligands journal, February 2003

Nucleosome Repositioning via Loop Formation journal, May 2003

A coarse grain model for DNA journal, February 2007

Nucleosome hopping and sliding kinetics determined from dynamics of single chromatin fibers in Xenopus egg extracts journal, August 2007

A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. journal, September 1988

Coarse-grained modeling of DNA curvature journal, October 2014

A 'loop recapture' mechanism for ACF-dependent nucleosome remodeling journal, July 2005

Polymer Reptation and Nucleosome Repositioning text, January 2001

SSAGES : Software Suite for Advanced General Ensemble Simulations text, January 2018

Coarse-grained Modeling of DNA Curvature text, January 2014

Polymer reptation and nucleosome repositioning text, January 2001

Nucleosome repositioning via loop formation text, January 2002

MRI of Iatrogenic Spinal Epidermoid Tumor journal, November 1993

Intrinsic map dynamics exploration for uncharted effective free-energy landscapes
journal, June 2017

Structure and dynamics of DNA loops on nucleosomes studied with atomistic, microsecond-scale molecular dynamics
journal, April 2016

Blocking Transcription Through a Nucleosome with Synthetic DNA Ligands
journal, August 2002

In silico evidence for sequence-dependent nucleosome sliding
journal, October 2017

Determination of reaction coordinates via locally scaled diffusion map
journal, March 2011

Human diseases with underlying defects in chromatin structure and modification
journal, October 2001

Dynamics of Nucleosome Invasion by DNA Binding Proteins
journal, August 2011

A genomic code for nucleosome positioning
journal, July 2006

Evaluation of Dimensionality-Reduction Methods from Peptide Folding–Unfolding Simulations
journal, April 2013

Chromatin remodeling by DNA bending, not twisting
journal, January 2005

A Global Geometric Framework for Nonlinear Dimensionality Reduction
journal, December 2000

Mesoscale Simulation and Machine Learning of Asphaltene Aggregation Phase Behavior and Molecular Assembly Landscapes
journal, April 2017

Covalent modifications of histones during development and disease pathogenesis
journal, November 2007

Simplifying the representation of complex free-energy landscapes using sketch-map
journal, July 2011

Diffusion maps
journal, July 2006

Principal Component Analysis
book, January 1986

An experimentally-informed coarse-grained 3-site-per-nucleotide model of DNA: Structure, thermodynamics, and dynamics of hybridization
journal, October 2013

Artificial nucleosome positioning sequences.
journal, October 1989

Frustration, specific sequence dependence, and nonlinearity in large-amplitude fluctuations of allosteric proteins
journal, February 2011

Rapid Exploration of Configuration Space with Diffusion-Map-Directed Molecular Dynamics
journal, July 2013

Nonlinear Machine Learning of Patchy Colloid Self-Assembly Pathways and Mechanisms
journal, April 2014

The structure of DNA in the nucleosome core
journal, May 2003

A Mesoscale Model of DNA and Its Renaturation
journal, March 2009

Polymer Reptation and Nucleosome Repositioning
journal, May 2001

Geometric diffusions as a tool for harmonic analysis and structure definition of data: Multiscale methods
journal, May 2005

Systematic characterization of protein folding pathways using diffusion maps: Application to Trp-cage miniprotein
journal, February 2015

The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats
journal, November 1989

Nonlinear Dimensionality Reduction by Locally Linear Embedding
journal, December 2000

Rapid spontaneous accessibility of nucleosomal DNA
journal, December 2004

SSAGES: Software Suite for Advanced General Ensemble Simulations
journal, January 2018

Crystal structure of the nucleosome core particle at 2.8 Å resolution
journal, September 1997

Crystal Structures of Nucleosome Core Particles in Complex with Minor Groove DNA-binding Ligands
journal, February 2003

Nucleosome Repositioning via Loop Formation
journal, May 2003

A coarse grain model for DNA
journal, February 2007

Nucleosome hopping and sliding kinetics determined from dynamics of single chromatin fibers in Xenopus egg extracts
journal, August 2007

A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes.
journal, September 1988

Coarse-grained modeling of DNA curvature
journal, October 2014

A 'loop recapture' mechanism for ACF-dependent nucleosome remodeling
journal, July 2005

Polymer Reptation and Nucleosome Repositioning
text, January 2001

SSAGES : Software Suite for Advanced General Ensemble Simulations
text, January 2018

Coarse-grained Modeling of DNA Curvature
text, January 2014

Polymer reptation and nucleosome repositioning
text, January 2001

Nucleosome repositioning via loop formation
text, January 2002

MRI of Iatrogenic Spinal Epidermoid Tumor
journal, November 1993