Home

About

Advanced Search

Browse by Discipline

Scientific Societies

E-print Alerts

Add E-prints

E-print Network
FAQHELPSITE MAPCONTACT US


  Advanced Search  

 
Nuclear Hormone Receptor Targeted Virtual Screening Matthieu Schapira,* Ruben Abagyan, and Maxim Totrov
 

Summary: Nuclear Hormone Receptor Targeted Virtual Screening
Matthieu Schapira,* Ruben Abagyan, and Maxim Totrov
Molsoft LLC, 3366 North Torrey Pines Court, Suite 300, La Jolla, California 92037
Received January 9, 2003
Virtual library screening (VLS) is emerging as a valuable drug lead discovery tool. ICM-VLS
implementation of this technology was evaluated on a benchmark set of nuclear hormone
receptors (NRs), an important therapeutic target family. Over 5000 structurally diverse
compounds, including 78 known NR ligands, were screened against 18 crystal structures and
one computer model of 10 NR ligand binding domains in their active or inactive states. The
results confirm the ability of the VLS method to generate highly focused subsets of the input
chemical library, enriched 33- to 100-fold for all but one receptor studied. However, receptor
flexibility remains to be fully addressed, and the choice of the specific conformation used for
screening may determine the success of the exercise. We observe that for a particular ligand
VLS can often identify the correct target within the receptor family, although the technology
is unable to reliably discriminate between the closely related receptor isoforms. Additionally,
our results suggest that VLS may be applied successfully without an experimental structure
of the receptor by using a homology model. These data represent a realistic snapshot of the
state-of-the-art of NR-targeted VLS and define the recent progress and the remaining limitations
of the technology.
Introduction

  

Source: Abagyan, Ruben - School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego

 

Collections: Biology and Medicine