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 Concept Videos

You might also read

Related Articles

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

Sort by
Same author

Global genomic diversity of the selfing nematode <i>Caenorhabditis tropicalis</i> correlates with geography.

bioRxiv : the preprint server for biology·2026
Same author

Discovery and development of potent and selective dual NUAK/MARK inhibitors as Hippo pathway modulators for the treatment of cancer.

European journal of medicinal chemistry·2026
Same author

pH Sensitivity of the SERF1a Conformational Ensemble.

ACS omega·2026
Same author

Competition between glycine and GABA<sub>A</sub> receptors for gephyrin controls their equilibrium populations at inhibitory synapses.

Proceedings of the National Academy of Sciences of the United States of America·2025
Same author

<i>Caenorhabditis briggsae</i> ancestral genomic hyper-diversity contrasts with globally distributed genome-wide haplotypes.

bioRxiv : the preprint server for biology·2025
Same author

Modulation of SARS-CoV-2 spike binding to ACE2 through conformational selection.

Nature nanotechnology·2025

Related Experiment Video

Updated: Sep 3, 2025

A Semi-Quantitative Drug Affinity Responsive Target Stability DARTS assay for studying Rapamycin/mTOR interaction
05:28

A Semi-Quantitative Drug Affinity Responsive Target Stability DARTS assay for studying Rapamycin/mTOR interaction

Published on: August 27, 2019

16.6K

A Curvilinear-Path Umbrella Sampling Approach to Characterizing the Interactions Between Rapamycin and Three FKBP12

Dhananjay C Joshi1, Charlie Gosse2, Shu-Yu Huang1

  • 1Research Center for Applied Sciences, Academia Sinica, Taipei, Taiwan.

Frontiers in Molecular Biosciences
|July 25, 2022
PubMed
Summary

This study investigates the binding mechanism of rapamycin with FKBP12 using advanced simulations. It reveals distinct roles for hydrogen bonds in stabilizing the FKBP12-rapamycin complex, with D37 being crucial and Y82 less so.

Keywords:
FKBP12free energy calculationhydrogen bondmolecular dynamicsrapamycinumbrella sampling simulations

More Related Videos

Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases
06:56

Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases

Published on: September 6, 2024

461
Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

10.9K

Related Experiment Videos

Last Updated: Sep 3, 2025

A Semi-Quantitative Drug Affinity Responsive Target Stability DARTS assay for studying Rapamycin/mTOR interaction
05:28

A Semi-Quantitative Drug Affinity Responsive Target Stability DARTS assay for studying Rapamycin/mTOR interaction

Published on: August 27, 2019

16.6K
Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases
06:56

Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases

Published on: September 6, 2024

461
Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

10.9K

Area of Science:

  • Biochemistry
  • Computational Biology
  • Pharmacology

Background:

  • Rapamycin is an immunosuppressant macrolide that inhibits mTOR kinase.
  • Rapamycin binds to FKBP12 before interacting with its target.
  • The energetic and mechanistic details of FKBP12-rapamycin interaction require further elucidation.

Purpose of the Study:

  • To extend computational simulations to protein-small molecule interactions, specifically the FKBP12•rapamycin complex.
  • To estimate binding free energies of rapamycin with wild-type FKBP12 and two mutants (D37V, Y82F).
  • To analyze the mechanistic details and the role of hydrogen bonds in the binding process.

Main Methods:

  • Utilized a multiple-walker umbrella sampling simulation approach.
  • Applied simulations to characterize protein-small molecule interaction energetics.
  • Calculated standard free energies of binding for wild-type and mutant FKBP12.

Main Results:

  • Calculated binding free energies closely matched experimental data.
  • Identified distinct roles for hydrogen bonds involving D37 and Y82.
  • Removal of D37's carboxylate group significantly destabilized the complex, while Y82's hydroxyl group was less critical.

Conclusions:

  • The study provides a detailed energetic and mechanistic understanding of the FKBP12•rapamycin complex.
  • Hydrogen bonds play differential roles in stabilizing the complex, with D37 being essential and Y82 having indirect stabilizing mechanisms.
  • Computational simulations are effective for characterizing protein-small molecule interactions.