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Related Concept Videos

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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,...
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
Cell-surface Signaling01:21

Cell-surface Signaling

Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Enzyme-linked Receptors01:00

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Related Experiment Video

Updated: Jul 3, 2026

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET
10:59

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET

Published on: August 17, 2022

CONFIRM: connecting fragments found in receptor molecules.

David C Thompson1, R Aldrin Denny, Ramaswamy Nilakantan

  • 1Wyeth Research, Chemical and Screening Sciences, 200 CambridgePark Drive, Cambridge, MA, 02140, USA.

Journal of Computer-Aided Molecular Design
|July 10, 2008
PubMed
Summary

A new algorithm, CONFIRM (Connecting Fragments Found in Receptor Molecules), efficiently links molecular fragments. This method aids in fragment-based de novo drug design by connecting fragments within a target binding site.

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Area of Science:

  • Computational chemistry
  • Drug discovery
  • Structural biology

Background:

  • Fragment-based drug design (FBDD) is a powerful strategy for identifying novel drug candidates.
  • Connecting small molecular fragments within a target binding site is a critical step in FBDD.
  • Existing methods for fragment linking can be computationally intensive and lack automation.

Purpose of the Study:

  • To introduce a novel algorithm, CONFIRM (Connecting Fragments Found in Receptor Molecules), for automated fragment molecule connection.
  • To validate the CONFIRM algorithm's performance on various test systems.
  • To discuss the general applicability of CONFIRM in fragment-based de novo drug design.

Main Methods:

  • Development of the CONFIRM algorithm, which searches a library of molecular bridges.
  • Matching bridge candidates to search criteria derived from fragment binding information.
  • Automated connection of fragments with selected bridges and subsequent docking into the target receptor.
  • Assessment of docking poses using root-mean-squared deviation and docking scores.

Main Results:

  • Successful validation of the CONFIRM algorithm across multiple test systems.
  • Demonstration of automated fragment connection and docking capabilities.
  • The algorithm effectively identifies and connects suitable molecular bridges.

Conclusions:

  • The CONFIRM algorithm presents a novel and automated approach for connecting fragment molecules.
  • This method shows significant potential for advancing fragment-based de novo drug design.
  • CONFIRM offers a valuable tool for accelerating the drug discovery process.