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

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

6.3K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
6.3K
Protein-Drug Binding: Mechanism and Kinetics01:16

Protein-Drug Binding: Mechanism and Kinetics

1.4K
Protein-drug binding refers to the interaction between drugs and proteins within the body. This binding process can occur intracellularly, involving drug interactions with enzymes or receptors within cells, or extracellularly, involving plasma proteins in the blood.
Various forces drive these interactions, including hydrogen bonds, hydrophobic interactions, ionic bonds, electrostatic interactions, and van der Waals forces. These bonds enable drugs to bind to specific sites on proteins,...
1.4K

You might also read

Related Articles

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

Sort by
Same author

Disruption of MCL1/BOK transmembrane interaction as a novel strategy to induce cell death in tumours.

Cell death & disease·2026
Same author

Sweet and Bright: Illuminating Glycoprotein-Mediated Endocytosis via Metabolic Labeling and NanoLuciferase.

ACS chemical biology·2026
Same author

Hypoplastic Left Heart Syndrome Cardiomyocytes Exhibit Intrinsic Stress Vulnerabilities and Augmented Stress Responses in vitro.

Stem cell reviews and reports·2026
Same author

Exploring the structure and dynamics of peptide nanodiscs through a synergistic approach with NMR spectroscopy, SAS and MD simulations.

Communications chemistry·2026
Same author

Drop-on-demand antimicrobial printed coatings loaded with a dehydroabietic acid derivative to prevent orthopedic implant infections.

Journal of materials chemistry. B·2026
Same author

Dimeric Polyphenol Effect on Liquid-Ordered and Liquid-Disordered Membranes: Combined Insights from Molecular Dynamics Simulation and Langmuir Balance Measurements.

Langmuir : the ACS journal of surfaces and colloids·2026

Related Experiment Video

Updated: Dec 9, 2025

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
08:49

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Published on: June 20, 2025

910

Rigorous Computational Study Reveals What Docking Overlooks: Double Trouble from Membrane Association in Protein

Saara Lautala1, Riccardo Provenzani2, Artturi Koivuniemi1

  • 1Drug Research Program, Division of Pharmaceutical Biosciences, University of Helsinki, P.O. Box 56, Viikinkaari 5 E, FI-00014 Helsinki, Finland.

Journal of Chemical Information and Modeling
|September 11, 2020
PubMed
Summary
This summary is machine-generated.

Drug design for protein kinase C (PKC) activation faces challenges. Molecular modeling revealed an intramolecular hydrogen bond in PYR-1gP hinders its binding to PKC, unlike HMI-1a3.

More Related Videos

A Liposome Membrane Permeability Assay for Investigating the Effects of Phosphatidylinositol Phosphate Groups on Membranotropic Action of Venom PLA2
10:31

A Liposome Membrane Permeability Assay for Investigating the Effects of Phosphatidylinositol Phosphate Groups on Membranotropic Action of Venom PLA2

Published on: September 26, 2025

264
Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
09:42

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes

Published on: January 16, 2016

9.3K

Related Experiment Videos

Last Updated: Dec 9, 2025

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
08:49

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Published on: June 20, 2025

910
A Liposome Membrane Permeability Assay for Investigating the Effects of Phosphatidylinositol Phosphate Groups on Membranotropic Action of Venom PLA2
10:31

A Liposome Membrane Permeability Assay for Investigating the Effects of Phosphatidylinositol Phosphate Groups on Membranotropic Action of Venom PLA2

Published on: September 26, 2025

264
Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
09:42

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes

Published on: January 16, 2016

9.3K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Protein kinase C (PKC) activation is a therapeutic target.
  • Diacylglycerol (DAG) mimetics are potential drugs for modulating PKC activity.
  • Previous DAG mimetic HMI-1a3 is effective but highly lipophilic.

Purpose of the Study:

  • To investigate the binding mechanism of a less lipophilic DAG mimetic, PYR-1gP, to PKC.
  • To understand why PYR-1gP shows diminished binding compared to computational predictions.
  • To highlight the importance of molecular dynamics simulations in drug design for membrane-associated proteins.

Main Methods:

  • Computational molecular modeling and molecular dynamics simulations.
  • Analysis of intramolecular hydrogen bonding in PYR-1gP.
  • Assessment of PYR-1gP's orientation and accessibility within a membrane environment.
  • Comparison with the binding of the lipophilic analogue HMI-1a3.

Main Results:

  • PYR-1gP forms an intramolecular hydrogen bond that obstructs its binding to PKC.
  • This hydrogen bond reorients PYR-1gP within the membrane, preventing proper access to the PKC C1 domain.
  • Molecular dynamics simulations revealed critical differences in membrane interaction compared to docking studies.
  • HMI-1a3, lacking this intramolecular bond, binds effectively.

Conclusions:

  • Intramolecular hydrogen bonding can significantly impair drug candidate efficacy.
  • Molecular dynamics simulations in a membrane environment are crucial for designing effective DAG mimetics targeting PKC.
  • This approach is vital for developing drugs targeting weakly membrane-associated proteins.