uu.seUppsala University Publications
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
On the precision of calculated solvent-accessible surface areas
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, The Linnaeus Centre for Bioinformatics.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
2007 (English)In: Acta Crystallographica Section D: Biological Crystallography, ISSN 0907-4449, E-ISSN 1399-0047, Vol. 63, no 2, 270-274 p.Article in journal (Refereed) Published
Abstract [en]

The fact that protein structures are dynamic by nature and that structure models determined by X-ray crystallography, electron microscopy (EM) and nuclear magnetic resonance (NMR) spectroscopy have limited accuracy limits the precision with which derived properties can be reported. Here, the issue of the precision of calculated solvent-accessible surface areas (ASAs) is addressed. A number of protein structures of different sizes were selected and the effect of random shifts applied to the atomic coordinates on ASA values was investigated. Standard deviations of the ASA calculations were found to range from ∼10 to ∼80  Å2. Similar values are obtained for a handful of cases in the Protein Data Bank (PDB) where `ensembles' of crystal structures were refined against the same data set. The ASA values for 69 hen egg-white lysozyme structures were calculated and a standard deviation of the ASA of 81  Å2 was obtained (the average ASA value was 6571  Å2). The calculated ASA values do not show any correlation with factors such as resolution or overall temperature factors. A molecular-dynamics (MD) trajectory of lysozyme was also analysed. The ASA values during the simulation covered a range of more than 800  Å2. If different programs are used, the ASA values obtained for one small protein show a spread of almost 600  Å2. These results suggest that in most cases reporting ASA values with a precision better than 10  Å2 is probably not realistic and a precision of 50–100  Å2 would seem prudent. The precision of buried surface-area calculations for complexes is also discussed.

Place, publisher, year, edition, pages
2007. Vol. 63, no 2, 270-274 p.
Keyword [en]
precision, solvent-accessible surface-area calculations, molecular dynamics
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-95502DOI: 10.1107/S0907444906044118ISI: 000243495700017PubMedID: 17242521OAI: oai:DiVA.org:uu-95502DiVA: diva2:169742
Available from: 2007-03-01 Created: 2007-03-01 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Applications of Structural Bioinformatics for the Structural Genomics Era
Open this publication in new window or tab >>Applications of Structural Bioinformatics for the Structural Genomics Era
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Structural bioinformatics deals with the analysis, classification and prediction of three-dimensional structures of biomacromolecules. It is becoming increasingly important as the number of structures is growing rapidly. This thesis describes three studies concerned with protein-function prediction and two studies about protein structure validation.

New protein structures are often compared to known structures to find out if they have a known fold, which may provide hints about their function. The functionality and performance of eleven fold-comparison servers were evaluated. None of the tested servers achieved perfect recall, so in practise a combination of servers should be used.

If fold comparison does not provide any hints about the function of a protein, structural motif searches can be employed. A survey of left-handed helices in known protein structures was carried out. The results show that left-handed helices are rare motifs, but most of them occur in active or ligand-binding sites. Their identification can therefore help to pinpoint potentially important residues.

Sometimes all available methods fail to provide hints about the function of a protein. Therefore, the potential of using docking techniques to predict which ligands are likely to bind to a particular protein has been investigated. Initial results show that it will be difficult to build a reliable automated docking protocol that will suit all proteins.

The effect of various phenomena on the precision of accessible surface area calculations was also investigated. The results suggest that it is prudent to report such values with a precision of 50 to 100 Å2.

Finally, a survey of register shifts in known protein structures was carried out. The identified potential register shifts were analysed and classified. A machine-learning approach ("rough sets") was used in an attempt to diagnose register errors in structures.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 86 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 275
Keyword
Bioinformatics, structural bioinformatics, fold comparison, left-handed helix, docking, solvent-accessible surface area, register shift, X-ray crystallography, Bioinformatik
Identifiers
urn:nbn:se:uu:diva-7593 (URN)978-91-554-6809-5 (ISBN)
Public defence
2007-03-23, B41, BMC, Husargatan 3, Uppsala, 13:00
Opponent
Supervisors
Available from: 2007-03-01 Created: 2007-03-01Bibliographically approved
2. Protein Folding and DNA Origami
Open this publication in new window or tab >>Protein Folding and DNA Origami
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this thesis, the folding process of the de novo designed polypeptide chignolin was elucidated through atomic-scale Molecular Dynamics (MD) computer simulations. In a series of long timescale and replica exchange MD simulations, chignolin’s folding and unfolding was observed numerous times and the native state was identified from the computed Gibbs free-energy landscape. The rate of the self-assembly process was predicted from the replica exchange data through a novel algorithm and the structural fluctuations of an enzyme, lysozyme, were analyzed.

DNA’s structural flexibility was investigated through experimental structure determination methods in the liquid and gas phase. DNA nanostructures could be maintained in a flat geometry when attached to an electrostatically charged, atomically flat surface and imaged in solution with an Atomic Force Microscope. Free in solution under otherwise identical conditions, the origami exhibited substantial compaction, as revealed by small angle X-ray scattering. This condensation was even more extensive in the gas phase.

Protein folding is highly reproducible. It can rapidly lead to a stable state, which undergoes moderate fluctuations, at least for small structures. DNA maintains extensive structural flexibility, even when folded into large DNA origami.

One may reflect upon the functional roles of proteins and DNA as a consequence of their atomic-level structural flexibility. DNA, biology’s information carrier, is very flexible and malleable, adopting to ever new conformations. Proteins, nature’s machines, faithfully adopt highly reproducible shapes to perform life’s functions robotically.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 43 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 724
Keyword
protein folding, Molecular Dynamics simulations, DNA origami
National Category
Biophysics
Research subject
Physics with specialization in Biophysics
Identifiers
urn:nbn:se:uu:diva-121549 (URN)978-91-554-7756-1 (ISBN)
Public defence
2010-04-20, B21, Husargatan 3, 751 24 Uppsala, BMC, 10:15 (English)
Opponent
Supervisors
Available from: 2010-03-29 Created: 2010-03-25 Last updated: 2011-03-04

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Novotny, MarianSeibert, MarvinKleywegt, Gerard

Search in DiVA

By author/editor
Novotny, MarianSeibert, MarvinKleywegt, Gerard
By organisation
Department of Cell and Molecular BiologyThe Linnaeus Centre for Bioinformatics
In the same journal
Acta Crystallographica Section D: Biological Crystallography
Biological Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 567 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