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 Experiment Videos

Efficacy and selectivity in flexible database docking.

R M Knegtel1, M Wagener

  • 1Department of Molecular Design and Informatics, N.V. Organon, Oss, The Netherlands. ronald.knegtel@vpharm.com

Proteins
|December 11, 1999
PubMed
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

Concurrent acute coronary and Takotsubo syndrome: two in one.

The international journal of cardiovascular imaging·2023
Same author

Prevalence of eosinophilic esophagitis: A multicenter study on a pediatric population evaluated at thirty-six Latin American gastroenterology centers.

Revista de gastroenterologia de Mexico (English)·2018
Same author

Wound infection secondary to snakebite.

South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde·2017
Same author

Cytomegalovirus infection in patients with sepsis due to bloodstream infections: lower risk and better outcomes in new versus already hospitalised intensive care unit admissions.

Anaesthesia and intensive care·2016
Same author

Cardiac biomarkers for infarct diagnosis and early exclusion of acute coronary syndrome.

Herz·2014
Same author

Outcome of imported liver allografts and impact on patient access to liver transplantation.

Transplantation proceedings·2006
Same journal

Engineered HSP90-MP65 Bivalent Fusion Antigen: A Novel Vaccine Candidate Against Invasive Candidiasis.

Proteins·2026
Same journal

Physics-Based Energy Functions for Computational Protein Design.

Proteins·2026
Same journal

Impact of Stabilizing Osmolytes on the Conformational Dynamics of Human and Rat Islet Amyloid Polypeptides.

Proteins·2026
Same journal

Stabilization of Bone Morphogenetic Protein-2 at Physiological pH: Contrasting Roles of CHAPS and Arginine in Aggregation Inhibition.

Proteins·2026
Same journal

Structural Insights Into the Function of Leishmania major Adenylosuccinate Lyase.

Proteins·2026
Same journal

Generalizing the Gaussian Network Model: Spanning-Tree Thermodynamics Shows Entropy-Driven KRAS Activation.

Proteins·2026
See all related articles

Flexible database docking effectively prioritizes screening libraries by reducing conformational sampling. However, accurately distinguishing between similar active and inactive compounds remains a challenge for DOCK 4.0.

Area of Science:

  • Computational Chemistry
  • Drug Discovery
  • Molecular Modeling

Background:

  • High-throughput screening (HTS) requires efficient methods to prioritize large compound libraries.
  • Flexible database docking offers a computational approach to identify potential drug candidates.
  • DOCK 4.0 is a widely used software for molecular docking simulations.

Purpose of the Study:

  • To evaluate the efficacy of flexible database docking using DOCK 4.0 for retrieving biologically active molecules.
  • To assess the impact of conformational and orientational sampling on retrieval accuracy.
  • To compare the performance of energy and chemical scoring functions in DOCK 4.0.

Main Methods:

  • Flexible docking simulations were performed using DOCK 4.0 against thrombin and progesterone receptor targets.

Related Experiment Videos

  • A database of approximately 1,000 compounds with known activities was used.
  • Enrichment of active molecules within the top-ranked docking poses was analyzed as a function of sampling parameters.
  • Energy and chemical scoring methods were evaluated for their discriminatory power.

    • Main Results:

    • Optimal enrichment of active molecules was achieved with limited conformational sampling (five conformations) and restricted binding site sampling.
    • Energy scoring showed higher enrichment for the progesterone receptor (64%), while chemical scoring excelled for thrombin (94%).
    • Both scoring schemes struggled to differentiate between active compounds and chemically similar inactive molecules, except for energy scoring on the progesterone receptor.

    Conclusions:

    • Flexible docking with DOCK 4.0 can effectively prioritize large screening databases with reduced computational cost.
    • The choice of scoring function is protein-dependent, influencing the success of virtual screening.
    • Discriminating between closely related active and inactive compounds remains a significant challenge in current docking methodologies.