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

Related Concept Videos

Drug-Receptor Bonds

Drug-Receptor Bonds

Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.
In...

Covalent Bonds

Covalent Bonds

Covalent Bonds

Covalent Bonds

Overview
When two atoms share electrons to complete their valence shells, they create a covalent bond. An atom's electronegativity—the force with which shared electrons are pulled towards an atom—determines how the electrons are shared. Molecules formed with covalent bonds can be either polar or nonpolar. Atoms with similar electronegativities form nonpolar covalent bonds; the electrons are shared equally. Atoms with different electronegativities share electrons unequally,...

Covalent Bonding and Lewis Structures

Covalent Bonding and Lewis Structures

Compared to ionic bonds, which results from the transfer of electrons between metallic and nonmetallic atoms, covalent bonds result from the mutual attraction of atoms for a “shared” pair of electrons.

Valence Bond Theory

Valence Bond Theory

Coordination compounds and complexes exhibit different colors, geometries, and magnetic behavior, depending on the metal atom/ion and ligands from which they are composed. In an attempt to explain the bonding and structure of coordination complexes, Linus Pauling proposed the valence bond theory, or VBT, using the concepts of hybridization and the overlapping of the atomic orbitals. According to VBT, the central metal atom or ion (Lewis acid) hybridizes to provide empty orbitals of suitable...

Valence Bond Theory

Valence Bond Theory

Overview of Valence Bond Theory

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

AI decodes protein-ligand binding.

Nature chemical biology·2026

Same author

Facilitating structure-based drug discovery with an artificial intelligence-driven virtual screening platform.

Nature protocols·2026

Same author

EpiMII: Structure-Aware Graph Neural Networks for MHC-II Epitope Generation.

Research (Washington, D.C.)·2026

Same author

Overcoming Resistance in the Androgen Receptor: Rational and Strategic Design of Advanced Antagonists.

Accounts of chemical research·2026

Same author

Targeting the intrinsically disordered AR-NTD through a machine learning-based enhanced sampling workflow.

Nature communications·2026

Same author

BioTD: An Online Database of Biotoxins.

Journal of chemical information and modeling·2026

Search research articles

Related Experiment Video

Updated: Jan 10, 2026

Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay

Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay

Published on: February 28, 2025

One-Shot Rational Design of Covalent Drugs with CovalentLab.

Xi Xue¹, Xiangying Liu^1,2, Xue Liu^1,2

¹State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, P. R. China.

|November 28, 2025

Summary

This summary is machine-generated.

CovalentLab is a new computational platform for designing targeted covalent drugs. It expands drug discovery by identifying novel binding sites and generating over 100,000 potential covalent molecules for various diseases.

Keywords:

GAC TRK covalent design platform database deep learning post-translational modification site prediction web server

More Related Videos

Creating Highly Specific Chemically Induced Protein Dimerization Systems by Stepwise Phage Selection of a Combinatorial Single-Domain Antibody Library

Creating Highly Specific Chemically Induced Protein Dimerization Systems by Stepwise Phage Selection of a Combinatorial Single-Domain Antibody Library

Published on: January 14, 2020

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

Related Experiment Videos

Last Updated: Jan 10, 2026

Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay

Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay

Published on: February 28, 2025

Creating Highly Specific Chemically Induced Protein Dimerization Systems by Stepwise Phage Selection of a Combinatorial Single-Domain Antibody Library

Creating Highly Specific Chemically Induced Protein Dimerization Systems by Stepwise Phage Selection of a Combinatorial Single-Domain Antibody Library

Published on: January 14, 2020

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

Area of Science:

Drug Discovery and Design
Computational Chemistry
Medicinal Chemistry

Background:

Targeted covalent drugs show great promise for disease treatment.
Current covalent drug design methods are limited to specific residues like serine and cysteine.
Most protein binding pockets contain residues amenable to covalent modification.

Purpose of the Study:

To develop an interactive computational platform, CovalentLab, for rational covalent ligand design.
To integrate ligand-based and warhead-based strategies into a unified workflow.
To expand the scope of covalent drug discovery beyond traditional binding sites.

Main Methods:

Developed a covalent binding site prediction model using ESM-2 with LoRA fine-tuning.
Enabled prediction and ranking of nine classes of covalent-binding residues based on reactivity.
Facilitated systematic attachment of 210 electrophilic warheads or user-defined warheads to ligands.

Main Results:

Generated a comprehensive library of over 100,000 covalent molecules across 95 targets.
Successfully applied CovalentLab to real-world targets, identifying validated bioactive compounds.
Demonstrated efficacy in identifying TRK orthosteric and GAC allosteric inhibitors.

Conclusions:

CovalentLab provides a versatile, publicly accessible resource for covalent drug discovery.
The platform expands druggable targets and accelerates the development of targeted covalent therapies.
Bridged gaps in covalent drug discovery by enabling rational design for a wider range of binding sites.