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Assembling a toolkit for computational dissection of dense protein systems

Nilsson, Daniel LU (2021)
Abstract
The cellular interior is a dense environment. Understanding how such an environment impacts the properties of proteins and other macromolecules, as well as how weak, non-specific interactions drive processes such as protein droplet formation through liquid-liquid phase separation, is a major challenge in biological physics. The complexity of this environment often makes experimental studies extremely challenging, leaving an important niche to be filled by simulation studies.

Simulations do, however, have their own set of challenges, and to use them to their full potential, a suitable set of computational tools must be developed. Such a toolset must include accurate yet computationally affordable force fields, computationally... (More)
The cellular interior is a dense environment. Understanding how such an environment impacts the properties of proteins and other macromolecules, as well as how weak, non-specific interactions drive processes such as protein droplet formation through liquid-liquid phase separation, is a major challenge in biological physics. The complexity of this environment often makes experimental studies extremely challenging, leaving an important niche to be filled by simulation studies.

Simulations do, however, have their own set of challenges, and to use them to their full potential, a suitable set of computational tools must be developed. Such a toolset must include accurate yet computationally affordable force fields, computationally efficient simulation algorithms, and analysis tools that allow for the extraction of meaningful information from the simulation results.

In this thesis, a number of tools for all three areas are developed and/or evaluated. We present an atom level, implicit solvent force field, as well as a coarse-grained continuous HP model which we use for droplet formation studies. We investigate sampling issues in field theory simulations with the complex Langevin equation. We use finite-size scaling analysis to analyse simulations of liquid-liquid phase separation, and Markov state modeling to analyse crowding simulations.
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Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Doctor Virnau, Peter, Johannes Gutenberg University Mainz, Germany
organization
publishing date
type
Thesis
publication status
published
subject
keywords
macromolecular crowding, liquid-liquid phase separation, Monte Carlo simulation, time-lagged independent component analysis, finite-size scaling, polymer field theory, protein force field, Fysicumarkivet A:2021:Nilsson
pages
128 pages
publisher
Lund University (Media-Tryck)
defense location
Lundmarksalen, Astronomihuset. Join via zoom: https://www.atp.lu.se/calendar/phd-defence-daniel-nilsson
defense date
2021-10-22 10:00:00
ISBN
978-91-8039-019-4
978-91-8039-018-7
language
English
LU publication?
yes
id
ee153d7a-7d74-4ab5-ab2d-3e16408be59f
date added to LUP
2021-09-22 16:01:56
date last changed
2022-08-18 10:49:09
@phdthesis{ee153d7a-7d74-4ab5-ab2d-3e16408be59f,
  abstract     = {{The cellular interior is a dense environment. Understanding how such an environment impacts the properties of proteins and other macromolecules, as well as how weak, non-specific interactions drive processes such as protein droplet formation through liquid-liquid phase separation, is a major challenge in biological physics. The complexity of this environment often makes experimental studies extremely challenging, leaving an important niche to be filled by simulation studies. <br/><br/>Simulations do, however, have their own set of challenges, and to use them to their full potential, a suitable set of computational tools must be developed. Such a toolset must include accurate yet computationally affordable force fields, computationally efficient simulation algorithms, and analysis tools that allow for the extraction of meaningful information from the simulation results.<br/><br/>In this thesis, a number of tools for all three areas are developed and/or evaluated. We present an atom level, implicit solvent force field, as well as a coarse-grained continuous HP model which we use for droplet formation studies. We investigate sampling issues in field theory simulations with the complex Langevin equation. We use finite-size scaling analysis to analyse simulations of liquid-liquid phase separation, and Markov state modeling to analyse crowding simulations.<br/>}},
  author       = {{Nilsson, Daniel}},
  isbn         = {{978-91-8039-019-4}},
  keywords     = {{macromolecular crowding; liquid-liquid phase separation; Monte Carlo simulation; time-lagged independent component analysis; finite-size scaling; polymer field theory; protein force field; Fysicumarkivet A:2021:Nilsson}},
  language     = {{eng}},
  publisher    = {{Lund University (Media-Tryck)}},
  school       = {{Lund University}},
  title        = {{Assembling a toolkit for computational dissection of dense protein systems}},
  url          = {{https://lup.lub.lu.se/search/files/102773552/Daniel_Nilsson_komplett.pdf}},
  year         = {{2021}},
}