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 Concept Videos

Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
Principles of Pharmacogenetics: Types of Genetic Variants01:27

Principles of Pharmacogenetics: Types of Genetic Variants

The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...

You might also read

Related Articles

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

Sort by
Same author

Quantitative phase microscopy for time-lapse hypoxia-induced cellular assays based on the transport of intensity equation.

Applied optics·2025
Same author

Single-shot 3 × 3 Mueller matrix microscopy with color polarization encoding.

Optics letters·2024
Same author

Differential effects of coverslip-induced hypoxia and cobalt chloride mimetic hypoxia on cellular stress, metabolism, and nuclear structure.

Tissue & cell·2024
Same author

Spatial perception in stereoscopic augmented reality based on multifocus sensing.

Optics express·2024
Same author

Real-time phase retrieval in division of aperture microscopy with the transport of intensity equation.

Journal of the Optical Society of America. A, Optics, image science, and vision·2024
Same author

Contributions of viral oncogenes of HPV-18 and hypoxia to oxidative stress and genetic damage in human keratinocytes.

Scientific reports·2023

Related Experiment Video

Updated: Jul 17, 2026

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein
11:23

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein

Published on: June 30, 2019

Molecular basis for specificity in the druggable kinome: sequence-based analysis.

Jianping Chen1, Xi Zhang, Ariel Fernández

  • 1Program in Applied Physics and Rice Quantum Institute, Rice University, Houston, TX 77005, USA.

Bioinformatics (Oxford, England)
|January 27, 2007
PubMed
Summary

Designing kinase inhibitors is challenging. This study reveals that targeting polar dehydration patterns, rather than ligand-kinase interactions, improves drug specificity and reduces off-target effects for better drug discovery.

More Related Videos

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
08:31

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Published on: December 1, 2020

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
07:08

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Published on: July 14, 2015

Related Experiment Videos

Last Updated: Jul 17, 2026

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein
11:23

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein

Published on: June 30, 2019

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
08:31

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Published on: December 1, 2020

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
07:08

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues

Published on: July 14, 2015

Area of Science:

  • Computational chemistry and structural biology
  • Drug discovery and medicinal chemistry
  • Bioinformatics and cheminformatics

Background:

  • Rational kinase inhibitor design faces challenges due to unclear molecular features dictating pharmacological impact and cross-reactivity.
  • Traditional factors like hydrophobic interactions and hydrogen bonding are insufficient for assessing kinase inhibitor specificity.
  • Understanding molecular similarity versus difference in kinase targets is crucial for predicting drug promiscuity and specificity.

Purpose of the Study:

  • To identify molecular features that govern specificity versus promiscuity in kinase inhibitors.
  • To develop a sequence-based classifier for predicting pharmacological differences among kinase targets.
  • To propose a novel strategy for designing kinase inhibitors with improved specificity.

Main Methods:

  • Analysis of a screened sample of the human pharmacokinome, including targets with unreported structures.
  • Development of a sequence-based classifier using a microenvironmental descriptor measuring dehydration propensities.
  • Quantification of water exclusion propensity around preformed polar pairs in kinase structures.

Main Results:

  • Drug designs promoting pairwise ligand-kinase interactions foster promiscuity due to conserved ATP-binding site features.
  • A novel structural marker based on dehydration propensities, localized in kinase loopy regions, enables accurate prediction of pharmacological differences.
  • Targeting polar dehydration patterns offers a more specific approach than promoting direct ligand-kinase interactions.

Conclusions:

  • Specificity in kinase inhibitor design can be enhanced by focusing on polar dehydration patterns rather than direct ligand-kinase interactions.
  • A sequence-based classifier utilizing dehydration propensities can predict pharmacological differences, guiding the development of more specific drugs.
  • This approach heralds a new generation of kinase inhibitors with improved control over specificity.