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

LEA3D: a computer-aided ligand design for structure-based drug design.

Dominique Douguet1, Hélène Munier-Lehmann, Gilles Labesse

  • 1Centre de Biochimie Structurale (CNRS UMR 5048, INSERM UMR U554), Faculté de Pharmacie, Université Montpellier I, 15, avenue Charles Flahault, 34060 Montpellier Cedex, France. douguet@cbs.cnrs.fr

Journal of Medicinal Chemistry
|April 2, 2005
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

SENSAAS-Bioisostere: A computational method for 3D shape-guided bioisosteric replacements and scaffold-hopping.

European journal of medicinal chemistry·2026
Same author

HTRF-based identification of small molecules targeting SARS-CoV-2 E protein interaction with ZO-1 PDZ2.

Scientific reports·2025
Same author

Exploring the multi-protein assembly of the enzymes of the de novo purine nucleotide biosynthetic pathway from Pseudomonas aeruginosa.

International journal of biological macromolecules·2025
Same author

Fragment-based drug design of a bacterial kinase inhibitor capable of increasing the antibiotic sensitivity of clinical isolates.

Communications chemistry·2025
Same author

Selective eIF4E-eIF4G Pairing and Cap-4 Recognition Mechanisms in Trypanosomatids: Insights From EIF4E5-EIF4G1 and EIF4E6-EIF4G5 Complexes.

Journal of molecular biology·2025
Same author

Design, synthesis, biophysical and biological evaluation of original condensed pyrrolopyrimidine and pyrrolopyridine ligands as anti-SARS-CoV-2 agents targeting G4.

European journal of medicinal chemistry·2025

The LEA3D software designs organic molecules using genetic algorithms and 3D fragments. This approach successfully generated 17 active compounds against Mycobacterium tuberculosis thymidine monophosphate kinase.

Area of Science:

  • Computational chemistry
  • Medicinal chemistry
  • Drug discovery

Background:

  • Rational drug design faces challenges with large combinatorial problems.
  • Genetic algorithms offer a viable approach for complex search spaces in drug design.

Purpose of the Study:

  • To introduce LEA3D, an enhanced program for designing organic molecules.
  • To utilize 3D fragment combination and a guided fitness function for de novo drug design.

Main Methods:

  • Development of LEA3D software combining 3D molecular fragments.
  • Implementation of a fitness function integrating multiple property evaluations, including FlexX docking scores.
  • Application to generate analogues of natural substrates for Mycobacterium tuberculosis thymidine monophosphate kinase.

Related Experiment Videos

Main Results:

  • The LEA3D program successfully conceived novel organic molecules.
  • Out of 22 tested compounds, 17 demonstrated inhibitory activity.
  • Inhibitory activity was observed in the micromolar range.

Conclusions:

  • LEA3D represents an effective tool for de novo drug design.
  • The software facilitates the optimization of molecular properties through guided search.
  • The study validates the potential of LEA3D in identifying novel drug candidates.