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

Electrostatic complementarity between proteins and ligands. 2. Ligand moieties

P L Chau1, P M Dean

  • 1Department of Pharmacology, University of Cambridge, U.K.

Journal of Computer-Aided Molecular Design
|October 1, 1994
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

Relational bodies.

Journal of law and medicine·2014
Same author

The pyridylthioacetmorpholides and pyridylacetic acids.

Journal of the American Chemical Society·2010
Same author

Chemical genomics: a challenge for de novo drug design.

Molecular biotechnology·2007
Same author

The impact of epilepsy surgery on quality of life in children.

Neurology·2006
Same author

Analysis methods for identifying coordinated movements during ligand unbinding.

Journal of computer-aided molecular design·2003
Same author

Reality hits postdocs earlier in France.

Nature·2001
Same journal

Topological data analysis for antibody-drug conjugate payload discovery: a computational framework for mechanistic classification and target validation.

Journal of computer-aided molecular design·2026
Same journal

Commentary on the fundamentals and development of artificial intelligence models in the life sciences and best research practices.

Journal of computer-aided molecular design·2026
Same journal

RANQSAR: a standalone open-source application for reproducible machine learning-based QSAR analysis.

Journal of computer-aided molecular design·2026
Same journal

Integrating evolutionary and compositional features with ML and DL for robust and interpretable druggable protein prediction.

Journal of computer-aided molecular design·2026
Same journal

QUAD: a composite risk framework integrating uncertainty, applicability domain, and model disagreement for reliable QSAR predictions.

Journal of computer-aided molecular design·2026
Same journal

Comparative quantum-chemical investigation of 2-chloro-N-(4-methoxyphenyl)acetamide and 2-(4-methoxyphenylamino)-2-oxoethyl meth/acrylate: DFT, TD-DFT, and non-covalent interaction analyses.

Journal of computer-aided molecular design·2026
See all related articles

Fragment-based drug design can lead to suboptimal electrostatic interactions. Optimizing electrostatic complementarity globally, rather than fragment by fragment, is crucial for effective ligand design.

Area of Science:

  • Computational chemistry
  • Medicinal chemistry
  • Drug discovery

Background:

  • Drug design often employs fragment-based strategies, sequentially building ligands within a receptor site.
  • Optimization is typically performed on individual fragments during this process.

Purpose of the Study:

  • To investigate whether sequential fragment optimization in drug design yields optimal electrostatic interactions.
  • To determine if whole-ligand electrostatic complementarity can be predicted from individual fragment complementarities.

Main Methods:

  • Calculation of electrostatic complementarities between ligand fragments (moieties) and the receptor site.
  • Comparison of whole-ligand complementarity with the sum or average of individual moiety complementarities.

Related Experiment Videos

Main Results:

  • Whole-ligand electrostatic complementarity is not the simple mathematical mean of individual moiety complementarities.
  • No straightforward relationship was found between moiety and whole-ligand electrostatic complementarities.
  • Predicting whole-ligand electrostatic complementarity from constituent parts using simple models is challenging.

Conclusions:

  • Current fragment-based drug design optimization strategies may not achieve optimal electrostatic interactions.
  • Drug design requires a global optimization approach for electrostatic complementarity, not a moiety-by-moiety method.