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

Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

11.1K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.1K
Machines01:19

Machines

581
Machines are complex structures consisting of movable, pin-connected multi-force members that work together to transmit forces. One example of a machine is the cutting plier, which is used to cut wires by applying forces to its handles. When equal and opposite forces are exerted on the handles of the cutting plier, they cause the cutting edges to come together and apply equal and opposite reaction forces on the wire, which are greater than the applied forces.
A free-body diagram of the...
581
The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

15.2K
The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
15.2K
Machines: Problem Solving II01:30

Machines: Problem Solving II

678
Machines are complex structures consisting of movable, pin-connected multi-force members that work together to transmit forces. Consider a lifting tong carrying a 100 kg load. It comprises movable sections DAF and CBG linked together with member AB.
678
Machines: Problem Solving I01:22

Machines: Problem Solving I

727
A toggle clamp is a mechanical device commonly used for holding and clamping objects in various applications, such as woodworking, metalworking, and assembly operations. Consider a toggle clamp subjected to a force of 200 N at the handle. The vertical clamping force can be calculated, provided the dimensions of the toggle clamp are known.
The toggle clamp system is a machine structure consisting of movable, pin-connected multi-force members that form a stabilized system to transmit forces. The...
727
Ligand Binding Sites02:40

Ligand Binding Sites

15.2K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
15.2K

You might also read

Related Articles

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

Sort by
Same author

Crowder-Induced Conformational Fluctuations Modulate the Phase Separation of the Yeast Sup35NM Domain.

Biomacromolecules·2026
Same author

Generative Machine Learning of Conformational Ensembles of Intrinsically Disordered Proteins: Progress and Opportunities.

Journal of chemical theory and computation·2026
Same author

Multisubstrate Allostery with a Single Helical Switch in Cytochrome P450cam.

The journal of physical chemistry letters·2025
Same author

Controlling Nanopore Dynamics via Loop Stapling and Unstapling for Tunable Substrate Transport.

ACS nano·2025
Same author

How good is generative diffusion model for enhanced sampling of protein conformations across scales and in all-atom resolution?

The Journal of chemical physics·2025
Same author

Pyrrole-Linked Benzimidazolyl Hydrazone Self-Assembly Forms HCl Channels and Induces Apoptosis in Cancer Cells.

Angewandte Chemie (International ed. in English)·2025
Same journal

Knowledge Distillation of a Protein Language Model Yields a Foundational Implicit Solvent Model.

Journal of chemical theory and computation·2026
Same journal

Generalizable Protein Folding Pathway Exploration with DA2-GRASP: Extending Beyond Miniproteins.

Journal of chemical theory and computation·2026
Same journal

Improving PCM in Protic Media: Markov State Models for TD-DFT Calculations.

Journal of chemical theory and computation·2026
Same journal

Efficient Coupled-Cluster Python Frameworks for Next-Generation GPUs: A Comparative Study of CuPy and PyTorch on the Hopper and Grace Hopper Architecture.

Journal of chemical theory and computation·2026
Same journal

Extending the MARTINI 3 Coarse-Grained Force Field to Polypeptoids.

Journal of chemical theory and computation·2026
Same journal

Statistical Mechanics of Density- and Temperature-Dependent Potentials: Application to Condensed Phases within GenDPDE.

Journal of chemical theory and computation·2026
See all related articles

Related Experiment Video

Updated: Feb 14, 2026

Analyzing Mitochondrial Morphology Through Simulation Supervised Learning
12:06

Analyzing Mitochondrial Morphology Through Simulation Supervised Learning

Published on: March 3, 2023

4.8K

Machine Learning and Computer Simulation Disentangle the Fuzzy Inhibitor Binding by Hsp90.

Mohammad Sahil1, Jaya Krishna Koneru1, Jagannath Mondal1

  • 1Tata Institute of Fundamental Research Hyderabad, 36/P Gopanapalli Village, Hyderabad TS-500046, India.

Journal of Chemical Theory and Computation
|February 13, 2026
PubMed
Summary
This summary is machine-generated.

We resolved the complex binding mechanism of geldanamycin to heat shock protein 90 (Hsp90) using advanced simulations and machine learning, revealing a key intermediate state crucial for drug design.

More Related Videos

Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
11:07

Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding

Published on: September 21, 2011

16.9K
Asthma Detection Research Based on Voice Signal Processing and Machine Learning
04:04

Asthma Detection Research Based on Voice Signal Processing and Machine Learning

Published on: July 22, 2025

1.1K

Related Experiment Videos

Last Updated: Feb 14, 2026

Analyzing Mitochondrial Morphology Through Simulation Supervised Learning
12:06

Analyzing Mitochondrial Morphology Through Simulation Supervised Learning

Published on: March 3, 2023

4.8K
Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
11:07

Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding

Published on: September 21, 2011

16.9K
Asthma Detection Research Based on Voice Signal Processing and Machine Learning
04:04

Asthma Detection Research Based on Voice Signal Processing and Machine Learning

Published on: July 22, 2025

1.1K

Area of Science:

  • Biophysics
  • Computational Chemistry
  • Structural Biology

Background:

  • Heat shock protein 90 (Hsp90) is a vital cancer target.
  • Conflicting crystallographic and NMR data for Hsp90 inhibitors complicate drug design.

Purpose of the Study:

  • To elucidate the binding mechanism of geldanamycin (GDM) to N-Hsp90.
  • To reconcile structural discrepancies in Hsp90 inhibitor binding models.

Main Methods:

  • >100 μs of all-atom molecular dynamics (MD) simulations.
  • Hybrid adaptive simulation strategies and τ-random acceleration MD.
  • Markov state modeling and funnel metadynamics simulations.
  • Explainable machine learning for mechanistic attribution.

Main Results:

  • A long-lived intermediate state dominates the GDM binding pathway to Hsp90.
  • The intermediate exhibits a 'loop-in' conformation before transitioning to the 'loop-out' bound state.
  • Binding free energies align with experimental data.
  • Machine learning identified distinct conformational selection and induced-fit mechanisms at the residue level.

Conclusions:

  • The study resolves longstanding structural discrepancies in Hsp90 inhibitor binding.
  • An intermediate-centric binding mechanism is proposed.
  • This framework offers a blueprint for targeting dynamic proteins like Hsp90.