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 Videos

Kinases, homology models, and high throughput docking.

David J Diller¹, Rixin Li

¹Pharmacopeia, Inc., CN5350, Princeton, New Jersey 08543-5350, USA. ddiller@pharmacop.com

Journal of Medicinal Chemistry

|October 17, 2003

Summary

High-throughput docking into protein homology models is valuable for drug discovery. This method successfully enriched known kinase inhibitors, demonstrating its potential for designing targeted drug libraries and improving selectivity.

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

Effects on RNA Quality of PBMCs Under Different Cryopreservation Times and Processing Methods in Patients with Advanced Non-Small Cell Lung Cancer.

Journal of visualized experiments : JoVE·2026

Same author

Real-world evidence on the efficacy, safety, and biomarkers of immunotherapy combined with radiotherapy in limited-stage small cell lung cancer.

Journal of thoracic disease·2026

Same author

Clinicopathological characteristics and therapeutic outcomes in patients with non-small cell lung cancer harboring <i>SMARCA4</i> mutations.

Annals of medicine·2026

Same author

Efficacy and safety analysis of treatment in patients with EGFR-mutated advanced NSCLC who progressed on TKIs: a systematic review and meta-analysis.

Frontiers in immunology·2025

Same author

A clinically translatable 2.5D lung adenocarcinoma organoid platform derived from malignant pleural effusions for precision drug screening and tumor-immune-stromal modeling.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie·2025

Same author

The pathogenic mutations in smokers with non-small cell lung cancer: a next-generation sequencing study.

Translational lung cancer research·2025

Area of Science:

Structural biology
Computational chemistry
Pharmacology

Background:

Genome sequencing yields numerous protein structures, but experimental determination is slow.
High-throughput crystallography will provide representative structures for most protein families.
Protein modeling is crucial for drug discovery, library design, and engineering target selectivity.

Purpose of the Study:

To assess the utility of high-throughput docking into homology models for drug discovery.
To evaluate the effectiveness of homology models in capturing crucial selectivity information.

Main Methods:

Docking a database of random compounds, including known inhibitors, into homology models of six kinases.
Scoring and ranking docked compounds to identify enriched known inhibitors.

Related Experiment Videos

Main Results:

Known inhibitors were enriched 4-5 fold in the top 5% of all docked compounds across five of six kinase models.
Known inhibitors were enriched 2-3 fold in the top 5% of scored kinase inhibitors, indicating selectivity prediction.
Homology models successfully identified key selectivity determinants for kinase targets.

Conclusions:

High-throughput docking into homology models is a viable strategy for identifying potential drug leads.
Homology models can provide valuable selectivity information, aiding in the design of targeted drug discovery efforts.
This approach supports the development of genome-wide selectivity strategies for protein targets.