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

Structure-based approaches to improve selectivity: CDK2-GSK3beta binding site analysis.

Anna Vulpetti1, Patrizia Crivori, Alexander Cameron

  • 1Nerviano Medical Sciences, Viale Pasteur 10, 20014 Nerviano (MI), Italy. anna.vulpetti@nervianoms.com

Journal of Chemical Information and Modeling
|September 27, 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

Cryo-EM structure of the human Kir7.1 channel reveals the molecular basis of snowflake vitreoretinal degeneration disease.

Communications biology·2026
Same author

Integrating <sup>19</sup>Focused Screening with Make-On-Demand Chemical Spaces for Enhanced Fragment Follow-Up.

ChemMedChem·2026
Same author

Clinical outcomes of bromelain-based enzymatic debridement (NexoBrid®): evidence from the Italian National Burn Database.

Burns : journal of the International Society for Burn Injuries·2026
Same author

Fragment-based discovery enables direct targeting of the melanoma oncogene MITF.

Nature communications·2025
Same author

Multiple carbamylation events are required for differential modulation of Cx26 hemichannels and gap junctions by CO<sub>2</sub>.

The Journal of physiology·2025
Same author

Dermal Substitute Integra for the Treatment of Mammalian Bite Injuries of Nose: a New Reconstructive Ladder.

Plastic and reconstructive surgery. Global open·2024
Same journal

tmGNN-XAI: An Explainable Graph Neural Network Tool for Predicting Electronic Properties of Transition Metal Complexes from SMILES.

Journal of chemical information and modeling·2026
Same journal

QSAR in the Browser: An Interactive Cheminformatics Web Application.

Journal of chemical information and modeling·2026
Same journal

FoldDoF: Utilizing the Primary Degrees of Freedom of Protein Backbone for Geometric Modeling and Generation.

Journal of chemical information and modeling·2026
Same journal

Derisking Affinity Optimization for Macrocycles and Cyclic Peptides: High-Precision Free Energy Simulations across Five Diverse Targets.

Journal of chemical information and modeling·2026
Same journal

An End-User Audit of Reproducibility, Data Leakage, and Overfitting of the Top-Ranked ADMET Prediction Models in TDC Leaderboards.

Journal of chemical information and modeling·2026
Same journal

PFASGroups: An Open-Source Framework for Automated Identification, Structural Classification, and Prioritization of Per- and Polyfluoroalkyl Substances.

Journal of chemical information and modeling·2026
See all related articles

Two computational methods, GRID/CPCA and GRIND/CPCA, visualized structural differences in CDK2 and GSK3beta proteins. These analyses identified key differences in ATP binding pockets, guiding the development of selective CDK2 inhibitors.

Area of Science:

  • Structural bioinformatics
  • Computational chemistry
  • Drug discovery

Background:

  • Understanding structural variations between related proteins is crucial for targeted drug design.
  • Consensus Principal Component Analysis (CPCA) combined with structural descriptors offers potential for visualizing these differences.

Purpose of the Study:

  • To evaluate and compare GRID/CPCA and GRIND/CPCA methods for visualizing structural differences between related proteins.
  • To identify potential sites for enhancing selectivity of CDK2 inhibitors against GSK3beta.

Main Methods:

  • Utilized GRID/CPCA and GRIND/CPCA (GRid-INdependent Descriptors) for structural analysis.
  • Compared ten crystal structures of CDK2/cyclin A and GSK3beta complexed with various inhibitors.
  • Focused on analyzing the ATP binding pockets of both enzymes.

Related Experiment Videos

Main Results:

  • Highlighted significant structural differences in the posterior regions of the ATP binding pockets between CDK2 and GSK3beta.
  • Identified the gatekeeper residue (Phe80 in CDK2 vs. Leucine in GSK3beta) and Ala144 (vs. Cysteine) as key differentiating factors.
  • Observed that CDK2 possesses a less elongated and flatter buried region at the back of its ATP pocket compared to GSK3beta.

Conclusions:

  • The identified structural differences in the ATP binding pockets can guide the optimization of selective kinase inhibitors.
  • The study successfully guided the optimization towards a selective benzodipyrazole CDK2 inhibitor based on these structural insights.