Nuclear hormone receptor targeted virtual screening.

Evaluation of Virtual Screening as a Tool for Chemical Genetic Applications

A collection of over 50,000 functionally annotated drugs, clinical candidates, and endogenous ligands was docked in silico against nine binding sites from seven protein targets, representing diverse function and structure, namely the sulfotransferases SULT1E1 and SULT1A3, the histone methyltransferase EHMT1, the histone acetyltransferase MYST3, and the nuclear hormone receptors ERalpha, PPARgam...

Molecular Docking Based on Virtual Screening, Molecular Dynamics and Atoms in Molecules Studies to Identify the Potential Human Epidermal Receptor 2 Intracellular Domain Inhibitors

Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family having tyrosine kinase activity. Overexpression of HER2 usually causes malignant transformation of cells and is responsible for the breast cancer. In this work, the virtual screening, molecular docking, quantum mechanics and molecular dynamics methods were employed to study protein–ligand ...

Rational discovery of novel nuclear hormone receptor antagonists.

Nuclear hormone receptors (NRs) are potential targets for therapeutic approaches to many clinical conditions, including cancer, diabetes, and neurological diseases. The crystal structure of the ligand binding domain of agonist-bound NRs enables the design of compounds with agonist activity. However, with the exception of the human estrogen receptor-alpha, the lack of antagonist-bound "inactive"...

Knowledge-Based Methods To Train and Optimize Virtual Screening Ensembles

Ensemble docking can be a successful virtual screening technique that addresses the innate conformational heterogeneity of macromolecular drug targets. Yet, lacking a method to identify a subset of conformational states that effectively segregates active and inactive small molecules, ensemble docking may result in the recommendation of a large number of false positives. Here, three knowledge-ba...

Identification of nuclear hormone receptor homologs by screening libraries with highly degenerate oligonucleotide probes.