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

12.6K
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...
12.6K
The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

12.8K
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:
12.8K
Conserved Binding Sites01:49

Conserved Binding Sites

4.1K
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...
4.1K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

4.7K
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...
4.7K

You might also read

Related Articles

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

Sort by
Same author

The SLC15A4-LAMTOR1 interaction licenses endolysosomal TLR-mediated mTOR signaling and inflammatory cytokine production.

bioRxiv : the preprint server for biology·2026
Same author

Author Correction: Posttranslational modifications remodel proteome-wide ligandability.

Nature chemical biology·2026
Same author

Genetic and pharmacological inactivation of peptidoglycan remodeling increases antibiotic susceptibility of vancomycin-resistant Enterococcus faecium.

Nature communications·2026
Same author

Posttranslational modifications remodel proteome-wide ligandability.

Nature chemical biology·2026
Same author

Genetic and pharmacological inactivation of peptidoglycan remodeling increases antibiotic susceptibility of vancomycin-resistant <i>Enterococcus faecium</i>.

bioRxiv : the preprint server for biology·2026
Same author

Pharmacological Inhibition of SLC33A1 Promotes Endoplasmic Reticulum Hyperoxidation and Induces Adaptive IRE1/XBP1s Signaling.

bioRxiv : the preprint server for biology·2026

Related Experiment Video

Updated: May 26, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

288

Docking guidance with experimental ligand structural density improves docking pose prediction and virtual screening

Althea T Hansel-Harris1, Andreas F Tillack1, Diogo Santos-Martins1

  • 1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California, USA.

Protein Science : a Publication of the Protein Society
|February 25, 2025
PubMed
Summary

CryoXKit leverages experimental density from cryo-electron microscopy (cryo-EM) and X-ray crystallography (XRC) to improve molecular docking accuracy. This tool enhances pose prediction and virtual screening for drug design without needing expert intervention or pharmacophore definitions.

Keywords:
autodockdockingdrug discoveryvirtual screening

More Related Videos

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps
09:30

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Published on: July 19, 2024

1.2K
Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.3K

Related Experiment Videos

Last Updated: May 26, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

288
Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps
09:30

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Published on: July 19, 2024

1.2K
Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.3K

Area of Science:

  • Structural Biology
  • Computational Chemistry
  • Drug Discovery

Background:

  • High-resolution macromolecule structures from X-ray crystallography (XRC) and cryo-electron microscopy (cryo-EM) are abundant, offering valuable insights for drug design.
  • Current methods often rely on atomic coordinates for docking, overlooking the rich information contained within experimental density maps.
  • Directly utilizing density information can bypass the need for expert interpretation of coordinates and identify potential ligand-binding regions more comprehensively.

Purpose of the Study:

  • To develop a novel computational tool, CryoXKit, for integrating experimental density data into molecular docking workflows.
  • To assess the performance improvements offered by CryoXKit in pose prediction tasks like re-docking and cross-docking.
  • To evaluate the impact of CryoXKit-enhanced poses on the discriminatory power of virtual screening campaigns.

Main Methods:

  • CryoXKit was developed to incorporate experimental densities (from cryo-EM or XRC) as a biasing potential on heavy atoms during docking.
  • The tool was integrated with AutoDock-GPU for docking simulations.
  • Performance was evaluated using re-docking and cross-docking tasks, and virtual screening against the LIT-PCBA dataset.

Main Results:

  • Docking with CryoXKit guidance showed significant improvements in re-docking and cross-docking accuracy compared to standard AutoDock4.
  • Failures in cross-docking highlighted limitations in transferring information between different protein-ligand complexes.
  • Rescoring of improved poses from CryoXKit-assisted docking enhanced discriminatory power in virtual screening for specific targets.

Conclusions:

  • CryoXKit offers a user-friendly and computationally inexpensive method to enhance molecular docking performance using experimental density data.
  • The tool requires no prior pharmacophore definition, simplifying the docking process.
  • CryoXKit represents a valuable advancement for drug design by effectively leveraging structural density information.