Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Modeling conformational changes in cyclosporin A

M F O'Donohue1, A W Burgess, M D Walkinshaw

  • 1Ludwig Institute of Cancer Research, P.O. Royal Melbourne Hospital, Parkville, Vic, Australia.

Protein Science : a Publication of the Protein Society
|October 1, 1995
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

The complex mediators of cell growth and differentiation.

Immunology today·2014
Same author

The control of blood cell production.

Immunology today·2014
Same author

Different APC genotypes in proximal and distal sporadic colorectal cancers suggest distinct WNT/β-catenin signalling thresholds for tumourigenesis.

Oncogene·2012
Same author

Affinity purification of plasma membranes.

Journal of biomolecular techniques : JBT·2009
Same author

Recruitment of adenomatous polyposis coli and beta-catenin to axin-puncta.

Oncogene·2008
Same author

Ligand discovery and virtual screening using the program LIDAEUS.

British journal of pharmacology·2007
Same journal

Macromolecular crowding inhibits degradation of alpha-synuclein amyloid fibrils induced by cathepsins and MMP9.

Protein science : a publication of the Protein Society·2026
Same journal

Sequence-encoded differences in the conformational ensembles of CITED transcriptional activation domains impact coactivator binding.

Protein science : a publication of the Protein Society·2026
Same journal

The phospholipid biosynthesis enzyme PlsB contains three distinct domains for membrane association, lysophosphatidic acid synthesis, and dimerization.

Protein science : a publication of the Protein Society·2026
Same journal

Structural basis of ligand selectivity in FAD/NAD(P)H-dependent dehydrogenases: insights from trypanothione reductase and type II NADH dehydrogenase.

Protein science : a publication of the Protein Society·2026
Same journal

Achieving protease substrate-specific inhibition by mAb dual functional selections.

Protein science : a publication of the Protein Society·2026
Same journal

How important are quantum mechanical effects in controlling biological functions: Enzymes, electron transfer and bird navigation.

Protein science : a publication of the Protein Society·2026
See all related articles

Computer simulations revealed how the immunosuppressant cyclosporin A (CsA) transitions between its free and cyclophilin-bound conformations. This conformational change involves specific peptide bond alterations and side-chain movements, offering insights into drug binding dynamics.

Area of Science:

  • * Molecular dynamics simulations
  • * Computational chemistry
  • * Structural biology

Background:

  • * Cyclosporin A (CsA) is an immunosuppressant drug.
  • * NMR and X-ray structures show distinct free and cyclophilin-bound conformations of CsA.
  • * Understanding CsA's conformational flexibility is crucial for its mechanism of action.

Purpose of the Study:

  • * To investigate the molecular dynamics and conformational transitions of CsA.
  • * To elucidate the pathway between the free and bound conformations of CsA.
  • * To confirm the stability of different CsA conformations under various conditions.

Main Methods:

  • * Molecular dynamics simulations of CsA in water and vacuum at room temperature and 600 K.
  • * Analysis of conformational changes, including peptide bond isomerization and side-chain rearrangements.

Related Experiment Videos

  • * Calculation of backbone Root Mean Square Deviation (RMSD) to compare conformations.

    • Main Results:

    • * CsA's free and bound conformations are stable at room temperature.
    • * At elevated temperatures (600 K) in vacuum, a transition pathway from the free to the bound conformation was observed.
    • * The transition involves cis-trans isomerization of the MeLeu-9 peptide bond and rearrangement of hydrophobic side chains.
    • * The resulting conformation closely resembles the bound state (0.53 Å RMSD) and exhibits similar stability.

    Conclusions:

    • * A detailed pathway for CsA's conformational transition has been identified.
    • * Two distinct regions of coordinated movement within CsA were found to transition independently.
    • * These findings provide a deeper understanding of CsA's structural dynamics and its interaction with cyclophilin.