Related Experiment Video

Updated: Jan 30, 2026

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

1.2K

Discovery of Novel Androgen Receptor Ligands by Structure-based Virtual Screening and Bioassays

Wenfang Zhou1, Mojie Duan2, Weitao Fu3

  • 1College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; State Key Laboratory of Computer Aided Design and Computer Graphics (CAD&GC), Zhejiang University, Hangzhou 310058, China.

Genomics, Proteomics & Bioinformatics
|January 15, 2019
PubMed

Insights

Researchers identified novel androgen receptor (AR) ligands using virtual screening. Two compounds, HBP1-51 (agonist) and HBP1-58 (antagonist), show potent binding, offering potential for AR-related disease therapeutics.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Androgen receptor (AR) is crucial in diseases like prostate cancer.
  • AR ligand binding induces conformational changes affecting signaling.
  • Targeting AR with novel ligands offers therapeutic potential.

Purpose of the Study:

  • To discover novel androgen receptor (AR) ligands.
  • To identify compounds with high affinity for the AR ligand-binding domain (LBD).
  • To characterize the agonist/antagonist activity and binding mechanisms of new ligands.

Main Methods:

  • Docking-based virtual screening of diverse compounds.
  • AR-LBD affinity assays to identify binders.
  • Bioactivity assays, molecular dynamics (MD) simulations, and principal components analysis (PCA).

Main Results:

  • Five compounds showed strong binding to AR-LBD.
  • HBP1-51 and HBP1-58 exhibited potent AR binding (IC50 < enzalutamide).
  • HBP1-51 acts as an AR agonist, HBP1-58 as an AR antagonist, with distinct conformational changes observed.

Conclusions:

  • A virtual screening approach efficiently identified novel AR ligands.
  • HBP1-51 and HBP1-58 are promising lead compounds for AR-related diseases.
  • Understanding ligand-induced conformational changes aids in therapeutic development.
Keywords:
AR agonistAR antagonistAR ligandAndrogen receptorVirtual screening

More Related Videos

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery06:26

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery

Published on: May 16, 2021

5.5K
An ELISA Based Binding and Competition Method to Rapidly Determine Ligand-receptor Interactions08:40

An ELISA Based Binding and Competition Method to Rapidly Determine Ligand-receptor Interactions

Published on: March 14, 2016

20.2K

Related Concept Videos

Internal Receptors01:31

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
74.6K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.6K
Metal-Ligand Bonds02:51

Metal-Ligand Bonds

The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
24.3K
Olfactory Receptors: Location and Structure01:03

Olfactory Receptors: Location and Structure

The process of olfaction, also known as the sense of smell, is a sophisticated chemical response system. The specialized sensory neurons that facilitate this process, known as olfactory receptor neurons, are situated in an upper segment of the nasal cavity, known as the olfactory epithelium. Olfactory sensory neurons are bipolar, with their dendrites extending from the epithelium's apex into the mucus that lines the nasal cavity. Airborne molecules, when inhaled, traverse the olfactory...
11.8K
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...
4.0K
Ligand Binding Sites02:40

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
15.0K