Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
NMR Refinement and Peptide Folding Using the GROMACS Software
Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Theory.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.ORCID iD: 0000-0002-7659-8526
2021 (English)In: Journal of Biomolecular NMR, ISSN 0925-2738, E-ISSN 1573-5001, Vol. 75, no 4-5, p. 143-149Article in journal (Refereed) Published
Abstract [en]

Nuclear magnetic resonance spectroscopy is used routinely for studying the three-dimensional structures and dynamics of proteins. Structure determination is usually done by adding restraints based upon NMR data to a classical energy function and performing restrained molecular simulations. Here we report on the implementation of a script to extract NMR restraints from a NMR-STAR file and export it to the GROMACS software. With this package, it is possible to model distance restraints, dihedral restraints, and orientation restraints. The output from the script is validated by performing simulations with and without restraints, including the ab initio refinement of one peptide.

Place, publisher, year, edition, pages
Springer Nature Springer Nature, 2021. Vol. 75, no 4-5, p. 143-149
Keywords [en]
Python, NMR-STAR, Force Field, Amber, Charmm
National Category
Biophysics Physical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-434243DOI: 10.1007/s10858-021-00363-zISI: 000634305400001PubMedID: 33778935OAI: oai:DiVA.org:uu-434243DiVA, id: diva2:1526301
Available from: 2021-02-06 Created: 2021-02-06 Last updated: 2024-01-15Bibliographically approved
In thesis
1. Polymer and Protein Physics: Simulations of Interactions and Dynamics
Open this publication in new window or tab >>Polymer and Protein Physics: Simulations of Interactions and Dynamics
2021 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Proteins can, without any exaggeration, be called the "building blocks of life". Their physical properties depend not only on the chemical structure but also on their geometric shape. In this thesis, I investigate protein geometry using several different methods.

We start with a coarse-graining model to study the general behavior of polymers. For this reason, we utilize an effective Hamiltonian that can describe the thermodynamic properties of polymer chains and reproduce secondary and tertiary structures. To investigate this model, I perform classical Monte Carlo simulations using my software package.

Another problem we address in this thesis is how to distinguish thermodynamic phases of proteins. The conventional definition of phases of polymer systems uses scaling laws. However, this method needs the chain's length to be varied, which is impossible to do with heteropolymers where the number of sites is one of the system's characteristics. We will apply renormalization group (RG) theory ideas to overcome this difficulty. We present a scaling procedure and an observable through which RG flow can define a certain polymer chain's phase.

Another part of the thesis is dedicated to the method of molecular dynamics. Our focus is on a novel experimental technique called Single Particle Imaging (SPI). The spatial orientation of the sample in this method is arbitrary. Scientists proposed to use a strong electric field to fix the orientation since most biological molecules have a non-zero dipole moment. Motivated by this, we investigate the influence of a strong electric field's ramping on the orientation of protein ubiquitin. For the same question of SPI and using the same protein, we study the reproducibility of unfolding it in a strong electric field. With the help of a new graph representation, I show different unfolding pathways as a function of the electric field's value and compare them with thermal and mechanical unfolding. I show that the RG flow observable can also detect the different ubiquitin unfolding pathways more simply.

The study described in this thesis has two types of results. One is a very concrete type, which can be utilized right away in the SPI experiments, like MS SPIDOC on the European XFEL. The other type of results are more theoretical and opens up a new field for further research. However, all of them contribute to protein science, an area vital for humanity's ability to protect us from threats such as the current COVID-19 pandemic.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2021. p. 126
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 2015
Keywords
polymers, proteins, Monte Carlo, molecular dynamics, phase diagram, renormalisation group, SPI, polymer effective model, coarse-graining
National Category
Biophysics
Research subject
Physics with specialization in Biophysics
Identifiers
urn:nbn:se:uu:diva-434275 (URN)978-91-513-1139-5 (ISBN)
Public defence
2021-03-26, Polhemsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:30 (English)
Opponent
Supervisors
Available from: 2021-03-04 Created: 2021-02-08 Last updated: 2021-03-29

Open Access in DiVA

fulltext(979 kB)344 downloads
File information
File name FULLTEXT01.pdfFile size 979 kBChecksum SHA-512
452aed8f26673288a3935d8fb9711b894fef32b4aa18be15160f16624e8827c429e5e42ee33806a20e8dd4f142c5741de440def7e1402e5f512ebedb8420243f
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedFull text (chemrxiv)

Authority records

Sinelnikova, AnnaVan der Spoel, David

Search in DiVA

By author/editor
Sinelnikova, AnnaVan der Spoel, David
By organisation
Materials TheoryComputational Biology and Bioinformatics
In the same journal
Journal of Biomolecular NMR
BiophysicsPhysical Chemistry

Search outside of DiVA

GoogleGoogle Scholar
Total: 344 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 342 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf