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...
The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

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:
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses 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...

You might also read

Related Articles

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

Sort by
Same author

Adversarial Sequence Mutations in AlphaFold and ESMFold Reveal Nonphysical Structural Invariance, Confidence Failures, and Concerns for Protein Design.

Computational and structural biotechnology journal·2026
Same author

Toward mechanistic virtual immune cells.

Nature biotechnology·2026
Same author

Understanding Substance Dependence: What Differentiates Addictive from Non-Addictive Drugs?

bioRxiv : the preprint server for biology·2026
Same author

A reliability-screened thalamocortical control-network phenotype tracks cocaine-use history in cocaine use disorder.

medRxiv : the preprint server for health sciences·2026
Same author

AlphaInterp: Mechanistic Interpretability of AlphaFold 3 Reveals How Evolutionary Information Shapes Protein Structure Prediction.

bioRxiv : the preprint server for biology·2026
Same author

PHENOCAUZ: Linking Human Symptoms, Drug Side Effects and Efficacy to Their Molecular Causes Using Mendelian Disease Biology.

bioRxiv : the preprint server for biology·2026

Related Experiment Video

Updated: Jul 8, 2026

Protein Target Prediction and Validation of Small Molecule Compound
10:21

Protein Target Prediction and Validation of Small Molecule Compound

Published on: February 23, 2024

Assessment of programs for ligand binding affinity prediction.

Ryangguk Kim1, Jeffrey Skolnick

  • 1Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, 250 14th Street, Atlanta, Georgia 30318, USA.

Journal of Computational Chemistry
|January 4, 2008
PubMed
Summary
This summary is machine-generated.

Current binding free energy prediction programs show poor performance in drug discovery simulations. These tools often fail to accurately rank ligand binding affinities, indicating a need for improved computational methods.

More Related Videos

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English
14:34

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English

Published on: April 3, 2026

A Protocol for Computer-Based Protein Structure and Function Prediction
16:41

A Protocol for Computer-Based Protein Structure and Function Prediction

Published on: November 3, 2011

Related Experiment Videos

Last Updated: Jul 8, 2026

Protein Target Prediction and Validation of Small Molecule Compound
10:21

Protein Target Prediction and Validation of Small Molecule Compound

Published on: February 23, 2024

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English
14:34

A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English

Published on: April 3, 2026

A Protocol for Computer-Based Protein Structure and Function Prediction
16:41

A Protocol for Computer-Based Protein Structure and Function Prediction

Published on: November 3, 2011

Area of Science:

  • Computational chemistry
  • Drug discovery
  • Molecular modeling

Background:

  • Accurate prediction of binding free energy is crucial for virtual screening and lead optimization in drug discovery.
  • Existing computational tools for binding free energy estimation require rigorous evaluation across diverse scenarios.

Purpose of the Study:

  • To assess the performance of popular binding free energy estimation programs (FlexX, X-Score, AutoDock, BLEEP).
  • To evaluate program accuracy in various docking and complex structure scenarios, including receptor deformation and ligand randomization.

Main Methods:

  • Tested four binding free energy estimation programs: FlexX, X-Score, AutoDock, and BLEEP.
  • Evaluated performance using cocrystallized complexes, cross-docking, and decoy sets with randomized ligands or unfolded receptors.

Main Results:

  • No program demonstrated satisfactory correlation between experimental and estimated binding free energies across all tested datasets.
  • A significant correlation was observed between ligand molecular weight and binding affinity, independent of prediction accuracy.
  • Programs sometimes ranked ligand affinities correctly even when specific ligand-receptor interactions were compromised, failing to distinguish decoys.

Conclusions:

  • Current binding free energy estimation programs lack the necessary components to accurately capture specific ligand-binding interactions.
  • The findings highlight limitations in computational approaches for drug discovery, suggesting a need for methodological advancements.