A method to explore protein side chain conformational variability using experimental data.

Show simple item record

dc.contributor.author Allison, Jane R
dc.contributor.author van Gunsteren, Wilfred F
dc.coverage.spatial Germany
dc.date.accessioned 2022-05-06T04:50:27Z
dc.date.available 2022-05-06T04:50:27Z
dc.date.issued 2009-12
dc.identifier.citation (2009). ChemPhysChem: a European journal of chemical physics and physical chemistry, 10(18), 3213-3228.
dc.identifier.issn 1439-4235
dc.identifier.uri https://hdl.handle.net/2292/59039
dc.description.abstract Experimentally measured values of molecular properties or observables of biomolecules such as proteins are generally averages over time and space, which do not contain sufficient information to determine the underlying conformational distribution of the molecules in solution. The relationship between experimentally measured NMR (3)J-coupling values and the corresponding dihedral angle values is a particularly complicated case due to its nonlinear, multiple-valued nature. Molecular dynamics (MD) simulations at constant temperature can generate Boltzmann ensembles of molecular structures that are free from a priori assumptions about the nature of the underlying conformational distribution. They suffer, however, from limited sampling with respect to time and conformational space. Moreover, the quality of the obtained structures is dependent on the choice of force field and solvation model. A recently proposed method that uses time-averaging with local-elevation (LE) biasing of the conformational search provides an elegant means of overcoming these three problems. Using a set of side chain (3)J-coupling values for the FK506 binding protein (FKBP), we first investigate the uncertainty in the angle values predicted theoretically. We then propose a simple MD-based technique to detect inconsistencies within an experimental data set and identify degrees of freedom for which conformational averaging takes place or for which force field parameters may be deficient. Finally, we show that LE MD is the best method for producing ensembles of structures that, on average, fit the experimental data.
dc.format.medium Print
dc.language eng
dc.publisher Wiley
dc.relation.ispartofseries Chemphyschem : a European journal of chemical physics and physical chemistry
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm
dc.subject Tacrolimus
dc.subject Tacrolimus Binding Proteins
dc.subject Anti-Bacterial Agents
dc.subject Algorithms
dc.subject Molecular Dynamics Simulation
dc.subject Generic health relevance
dc.subject Science & Technology
dc.subject Physical Sciences
dc.subject Chemistry, Physical
dc.subject Physics, Atomic, Molecular & Chemical
dc.subject Chemistry
dc.subject Physics
dc.subject averaging
dc.subject biomolecular simulations
dc.subject local elevation
dc.subject molecular dynamics
dc.subject NMR spectroscopy
dc.subject NUCLEAR-MAGNETIC-RESONANCE
dc.subject VICINAL COUPLING-CONSTANTS
dc.subject PANCREATIC TRYPSIN-INHIBITOR
dc.subject CONTINUOUS PROBABILITY-DISTRIBUTION
dc.subject MOLECULAR-DYNAMICS SIMULATIONS
dc.subject FK506 BINDING-PROTEIN
dc.subject ALPHA-AMINO ACIDS
dc.subject NMR-SPECTROSCOPY
dc.subject ROTATIONAL-ISOMERISM
dc.subject TORSION ANGLES
dc.subject 0307 Theoretical and Computational Chemistry
dc.subject 0202 Atomic, Molecular, Nuclear, Particle and Plasma Physics
dc.subject 0306 Physical Chemistry (incl. Structural)
dc.title A method to explore protein side chain conformational variability using experimental data.
dc.type Journal Article
dc.identifier.doi 10.1002/cphc.200900400
pubs.issue 18
pubs.begin-page 3213
pubs.volume 10
dc.date.updated 2022-04-28T03:43:50Z
dc.rights.holder Copyright: The author en
dc.identifier.pmid 19882615 (pubmed)
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/19882615
pubs.end-page 3228
pubs.publication-status Published
dc.rights.accessrights http://purl.org/eprint/accessRights/RetrictedAccess en
pubs.subtype Research Support, Non-U.S. Gov't
pubs.subtype Journal Article
pubs.elements-id 739614
pubs.org-id Science
pubs.org-id Biological Sciences
dc.identifier.eissn 1439-7641
pubs.record-created-at-source-date 2022-04-28


Files in this item

Find Full text

This item appears in the following Collection(s)

Show simple item record

Share

Search ResearchSpace


Browse

Statistics