Skip to main content
Researchdata.se

Starting structures and NMR and simulation relaxation data for the structural ensembles of Dengue protease NS2B/NS3pro

https://doi.org/10.5878/5wea-fk76
The dengue protease NS2B/NS3pro has been reported to adopt either an ‘open’ or a ‘closed’ conformation. We have developed a conformational filter that combines nuclear magnetic resonance (NMR) with molecular dynamics (MD) simulations to identify conformational ensembles that dominate in solution. Experimental values derived from relaxation parameters for the backbone and methyl side chains were compared with the corresponding back-calculated relaxation parameters of different conformational ensembles obtained from free MD simulations. Our results demonstrate a high prevalence for the ‘closed’ conformational ensemble while the ‘open’ conformation is absent, indicating that the latter conformation is most probably due to crystal contacts. Conversely, conformational ensembles in which the positioning of the co-factor NS2B results in a ‘partially’ open conformation, previously described in both MD simulations and X-ray studies, were identified by our conformational filter. Altogether, we believe that our approach allows for unambiguous identification of true conformational ensembles, an essential step for reliable drug discovery.
Download data and documentation (17 files / 6.5 MiB)

Data files

  • amber_input_simulation_parameters.in
    1.43 KiB
  • I.pdb
    297.56 KiB
  • II.pdb
    297.56 KiB
  • III.pdb
    297.56 KiB
  • IV.pdb
    297.48 KiB
  • S135A_G2_Methyl_Fig3.tsv
    20.49 KiB
  • S135A_NS2B_NOE_Fig2.tsv
    3.96 KiB
  • S135A_NS2B_R1_Fig2.tsv
    4.96 KiB
  • S135A_NS2B_R2_Fig2.tsv
    5.31 KiB
  • S135A_NS3_NOE_Fig2.tsv
    14 KiB
  • S135A_NS3_R1_Fig2.tsv
    14.11 KiB
  • S135A_NS3_R2_Fig2.tsv
    15.23 KiB
  • S135A_R1_Methyl_Fig3.tsv
    12.72 KiB

Documentation files

  • Agback-T-et-al-2023.pdf
    5.24 MiB
  • MetaData.txt
    1.71 KiB
  • README_dataFig2Fig3.txt
    5.85 KiB
  • README_startingstructures.txt
    384 Bytes

Citation and access

Data access level:

Creator/​Principal investigator(s):

  • Peter Agback - Swedish University of Agricultural Sciences - Department of Molecular Sciences

    Opens a new window at orcid.org.

    ORCIDOpens in a new tab
  • Tatiana Agback - Swedish University of Agricultural Sciences - Department of Molecular Sciences
  • Dmitry Lesovoy - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS - Department of Structural Biology
  • Xiao Han - Karolinska Institute - Department of Medicine
  • Alexander Lomzov - Institute of Chemical Biology and Fundamental Medicine SB RAS - Laboratory for Structural Biology
  • Renhua Sun - Karolinska Institute - Department of Medicine
  • Tatyana Sandalova - Karolinska Institute - Department of Medicine
  • Vladislav Orekhov - Gothenburg University - Swedish NMR Centre
  • Adnane Achour - Karolinska Institute - Department of Medicine

Research principal:

Principal's reference number:

  • SLU.molsci.2023.4.4..IÄ-12

Data contains personal data:

No

Citation:

Language:

Method and outcome

Time period(s) investigated:

Data format/​data structure:

Species and taxons:

Data collection Experiment

Mode of collection:

Experiment

Description of the mode of collection:

NMR and MD relaxation study of the NS2B/NS3pro protease of Dengue

Time period(s) for data collection:

2018 - 2022

Data collector:

Source of the data:

  • Biological samples

Sample

Name:

NS2B/NS3pro

Description of sample:

protease from Dengue

Instrument

Name:

NMR spectrometer

Description of the instrument:

600 and 800MHz spectrometers

Administrative information

Responsible department/​unit:

Department of Molecular Sciences

Other research principals:

Funding

Funding agency:

Award number:

ITM17-0218

Award title:

Innovative experimental modelling of dynamic protein states.

Funding agency:

Award number:

2021-05061

Funding agency:

Award number:

21 1605 Pj01H

Funding agency:

Award number:

2019-03561

Topic and keywords

Standard för svensk indelning av forskningsämnen 2025:

Keywords:

Publications

Citation:

Agback, T., Lesovoy, D., Han, X., Lomzov, A., Sun, R., Sandalova, T., Yu, V., Adnane Achour, O., Agback, P. (2023). Combined NMR and molecular dynamics conformational filter identifies unambiguously dynamic ensembles of Dengue protease NS2B/NS3pro. Communications Biology 6:1193.

Contact

Metadata

Version 1
doris
slu
Published: