Related Experiment Video
Updated: Jul 21, 2025
Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b
Published on: November 11, 2016
Inhibitor Trapping in N-Myristoyltransferases as a Mechanism for Drug Potency
Danislav S Spassov1, Mariyana Atanasova1, Irini Doytchinova1
1Department of Chemistry, Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria.
Predicting drug inhibitor potency for N-myristoyltransferase (NMT) depends on stabilizing its closed state. This stabilization traps inhibitors, offering a new in silico method for predicting drug effectiveness.
Area of Science:
- Computational biology
- Drug discovery
- Enzyme kinetics
Background:
- Predicting inhibitor potency is a major challenge in drug design.
- N-myristoyltransferase (NMT) plays a crucial role in biological processes.
- NMT exists in open and closed conformations essential for its catalytic cycle.
Purpose of the Study:
- To investigate the relationship between NMT conformation and inhibitor potency.
- To identify a novel approach for predicting inhibitor effectiveness in silico.
Main Methods:
- Molecular dynamics simulations were employed to analyze NMT-inhibitor interactions.
- The study focused on the conformational changes of NMT upon ligand binding.
Main Results:
- Inhibitor potency is determined by the ability to stabilize the closed conformation of NMT.
- Stabilizing the closed state effectively traps inhibitors, hindering their dissociation.
- Conformational stabilization strongly correlates with ligand activity and can predict potency.
Conclusions:
- In silico prediction of inhibitor potency may rely on modeling protein conformational changes rather than solely on binding energy.
- Understanding NMT's conformational dynamics offers a new strategy for rational drug design.
More Related Videos
10:28A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors
Published on: August 17, 2019
10:33Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
Published on: October 26, 2015
Related Concept Videos
01:30Enzyme Inhibition
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
01:16Protein-Drug Binding: Mechanism and Kinetics
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,...
00:46Feedback Inhibition
01:26Targets for Drug Action: Overview
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
01:22Protein-Drug Binding: Determination Methods
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...