Capturing a dynamically interacting inhibitor by paramagnetic NMR spectroscopy

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00503801" target="_blank" >RIV/61388963:_____/19:00503801 - isvavai.cz</a>
Alternative codes found
RIV/61388980:_____/19:00503801 RIV/68378050:_____/19:00505253 RIV/00216208:11310/19:10393722
Result on the web
<a href="https://pubs.rsc.org/en/content/articlelanding/2019/CP/C9CP00416E#!divAbstract" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2019/CP/C9CP00416E#!divAbstract</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/c9cp00416e" target="_blank" >10.1039/c9cp00416e</a>

Result language
angličtina
Original language name
Capturing a dynamically interacting inhibitor by paramagnetic NMR spectroscopy
Original language description
Transient and fuzzy intermolecular interactions are fundamental to many biological processes. Despite their importance, they are notoriously challenging to characterize. Effects induced by paramagnetic ligands in the NMR spectra of interacting biomolecules provide an opportunity to amplify subtle manifestations of weak intermolecular interactions observed for diamagnetic ligands. Here, we present an approach to characterizing dynamic interactions between a partially flexible dimeric protein, HIV-1 protease, and a metallacarborane-based ligand, a system for which data obtained by standard NMR approaches do not enable detailed structural interpretation. We show that for the case where the experimental data are significantly averaged to values close to zero the standard fitting of pseudocontact shifts cannot provide reliable structural information. We based our approach on generating a large ensemble of full atomic models, for which the experimental data can be predicted, ensemble averaged and finally compared to the experiment. We demonstrate that a combination of paramagnetic NMR experiments, quantum chemical calculations, and molecular dynamics simulations offers a route towards structural characterization of dynamic protein-ligand complexes.
Czech name
—
Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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