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

Ligand Binding Sites02:40

Ligand Binding Sites

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...
Ligand Binding Sites02:40

Ligand Binding Sites

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...
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...

You might also read

Related Articles

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

Sort by
Same author

Correction: Molecular subtypes and the (in vitro) response of glioblastoma to temozolomide.

BJC reports·2026
Same author

Machine learning, whole genome sequencing, and Mendelian randomization support a role of CRP on COVID-19 severity.

Molecular medicine (Cambridge, Mass.)·2026
Same author

Molecular subtypes and the (in vitro) response of glioblastoma to temozolomide.

BJC reports·2026
Same author

A Polypharmacology-Driven Approach to Alzheimer's Disease and Tauopathies: Rational Design, Synthesis and Characterization of Amino-Pyrazole-Based Multikinase (GSK-3β/FYN-α/DYRK1A) Inhibitors.

Journal of medicinal chemistry·2026
Same author

From comprehensive geriatric assessment to rapid bedside screening: comparing MPI and BRASS in predicting hospital outcomes in older adults - the S. Giovanni-Addolorata Hospital-SIGOT GRACE study.

BMC geriatrics·2026
Same author

Multi-parametric profiling of plasma-derived extracellular vesicles reveals a disease-associated molecular signature supporting a liquid biopsy approach in myelofibrosis.

Molecular medicine (Cambridge, Mass.)·2026

Related Experiment Video

Updated: Jun 24, 2026

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
07:33

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry

Published on: October 15, 2018

Exploring complex protein-ligand recognition mechanisms with coarse metadynamics.

Matteo Masetti1, Andrea Cavalli, Maurizio Recanatini

  • 1Computational Science, Department of Chemistry and Applied Biosciences, ETH Zurich, USI Campus, Via Giuseppe Buffi 13, CH-6900 Lugano, Switzerland.

The Journal of Physical Chemistry. B
|March 21, 2009
PubMed
Summary

This study introduces coarse metadynamics, combining docking and clustering with fewer variables, to reveal detailed protein-ligand docking mechanisms. This method accurately distinguishes poses and identifies transition states, offering insights into binding free energy.

More Related Videos

Structure-Guided Design and Development of Novel Cyclophilin A Inhibitors and Ganoderiol-F Derivatives: An In-Silico Approach
10:01

Structure-Guided Design and Development of Novel Cyclophilin A Inhibitors and Ganoderiol-F Derivatives: An In-Silico Approach

Published on: June 23, 2026

Related Experiment Videos

Last Updated: Jun 24, 2026

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
07:33

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry

Published on: October 15, 2018

Structure-Guided Design and Development of Novel Cyclophilin A Inhibitors and Ganoderiol-F Derivatives: An In-Silico Approach
10:01

Structure-Guided Design and Development of Novel Cyclophilin A Inhibitors and Ganoderiol-F Derivatives: An In-Silico Approach

Published on: June 23, 2026

Area of Science:

  • Computational Chemistry
  • Molecular Dynamics
  • Biochemistry

Background:

  • Metadynamics is a powerful simulation technique for studying molecular recognition at atomistic detail.
  • A limitation of metadynamics is the requirement for prior knowledge of all relevant slow degrees of freedom.
  • Understanding protein-ligand interactions is crucial in drug discovery and molecular biology.

Purpose of the Study:

  • To develop and validate a novel computational protocol for elucidating protein-ligand docking mechanisms.
  • To overcome the limitations of traditional metadynamics by using a reduced set of degrees of freedom.
  • To accurately distinguish between different binding poses and determine binding free energy.

Main Methods:

  • A hybrid approach combining docking/clustering with metadynamics, termed 'coarse metadynamics'.
  • Metadynamics simulations were performed using a subset of the necessary degrees of freedom.
  • Analysis of simulation trajectories to identify docking pathways and transition states.

Main Results:

  • The coarse metadynamics approach successfully provided full mechanistic insight into protein-ligand docking.
  • The protocol effectively differentiated between crystallographic and non-crystallographic poses of protein-ligand complexes.
  • The transition state of the full undocking mechanism was identified, providing an estimate of binding free energy.

Conclusions:

  • Coarse metadynamics offers a computationally efficient and effective strategy for studying protein-ligand interactions.
  • This method enhances the understanding of molecular recognition mechanisms and aids in pose prediction.
  • The protocol has significant implications for drug design and the accurate prediction of binding affinities.