Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Search research articles

Related Experiment Video

Updated: Jun 18, 2025

Large-Scale Screens of Metagenomic Libraries

Large-Scale Screens of Metagenomic Libraries

Published on: May 28, 2007

Identifying Artifacts from Large Library Docking.

Yujin Wu¹, Fangyu Liu¹, Isabella Glenn¹

¹Department of Pharmaceutical Chemistry, University of California, San Francisco, 94158, United States.

Biorxiv : the Preprint Server for Biology

|July 29, 2024

Summary

This summary is machine-generated.

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

Toward a Random Background for Ligand Optimization.

bioRxiv : the preprint server for biology·2026

Same author

The Selectivity Implications of Docking Libraries with Greater and Lesser Similarities to Bio-like Molecules.

Journal of medicinal chemistry·2026

Same author

Drug-Induced Phospholipidosis as an Artifact in Antiviral Drug Repurposing.

ACS omega·2026

Same author

Library docking for Cannabinoid-2 Receptor ligands.

bioRxiv : the preprint server for biology·2026

Same author

Large Library Docking for Polypharmacology.

Journal of medicinal chemistry·2026

Same author

The selectivity implications of docking libraries with greater and lesser similarities to bio-like molecules.

bioRxiv : the preprint server for biology·2026

Same journal

Layered social competition coordinates reproductive hierarchy formation in ants.

bioRxiv : the preprint server for biology·2026

Same journal

Combination epigenetic-targeted therapy increases the immunogenicity of poorly immunogenic sarcomas.

bioRxiv : the preprint server for biology·2026

Same journal

Loss of LanC-like proteins delays post-injury regeneration of aging skeletal muscles.

bioRxiv : the preprint server for biology·2026

Same journal

Integrative Transfer Network: Deep Transfer Learning Across Populations and Prediction Targets.

bioRxiv : the preprint server for biology·2026

Same journal

Confidence-supported label-free metabolic imaging with FPhaS phase autofluorescence microscopy.

bioRxiv : the preprint server for biology·2026

Same journal

Sequence-encoded autoinhibition couples mRNA decapping activity to phase separation.

bioRxiv : the preprint server for biology·2026

See all related articles

Computational drug discovery faces challenges with large libraries producing false positives. Rescoring top docking hits with orthogonal methods effectively identifies and removes these artifacts, improving the accuracy of virtual screening for drug development.

Area of Science:

Computational Chemistry
Drug Discovery
Biochemistry

Background:

Large-scale virtual screening via molecular docking is a powerful tool for identifying potential drug candidates.
Increasing library sizes in docking screens can lead to a higher prevalence of scoring function artifacts, or 'cheaters', among top-ranked compounds.
These artifacts can be rare but become more dominant as screening libraries expand, potentially hindering the identification of true ligands.

Purpose of the Study:

To investigate the efficacy of rescoring top-ranked molecules from docking screens using orthogonal methods to identify and filter out artifacts.
To explore the utility of implicit solvent models and absolute binding free energy perturbation (AB-FEP) as cross-validation filters.
To validate a novel strategy for improving the reliability of large-scale virtual screening results.

More Related Videos

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source

Published on: May 29, 2021

Coral Reef Arks: An In Situ Mesocosm and Toolkit for Assembling Reef Communities

Coral Reef Arks: An In Situ Mesocosm and Toolkit for Assembling Reef Communities

Published on: January 6, 2023

Related Experiment Videos

Last Updated: Jun 18, 2025

Large-Scale Screens of Metagenomic Libraries

Large-Scale Screens of Metagenomic Libraries

Published on: May 28, 2007

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source

Published on: May 29, 2021

Coral Reef Arks: An In Situ Mesocosm and Toolkit for Assembling Reef Communities

Coral Reef Arks: An In Situ Mesocosm and Toolkit for Assembling Reef Communities

Published on: January 6, 2023

Main Methods:

Retrospective validation of the rescoring approach across nine different biological targets.
Prospective application of the method to a large library docking screen against AmpC β-lactamase.
Synthesis and experimental enzyme inhibition assays of prioritized compounds identified through docking and rescoring.

Main Results:

The orthogonal rescoring method successfully deprioritized high-ranking non-binders in retrospective studies while preserving true ligands.
In the prospective AmpC β-lactamase study, none of the 39 compounds flagged as artifacts inhibited the enzyme.
Of the 89 compounds identified as plausible true actives, 57% showed enzyme inhibition, with 19 exhibiting potent activity (apparent IC50 < 1 µM).

Conclusions:

Rescoring top docking hits with orthogonal methods, such as implicit solvent models and AB-FEP, is an effective strategy for identifying and removing computational artifacts.
This approach significantly enhances the hit quality from large library docking screens, reducing false positives.
The proposed method holds promise for widespread adoption in drug discovery as screening libraries continue to grow.