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Summary: Improved docking, screening and selectivity prediction for small
molecule nuclear receptor modulators using conformational
ensembles
So-Jung Park · Irina Kufareva · Ruben Abagyan
Received: 8 December 2009 / Accepted: 26 April 2010
Ó The Author(s) 2010. This article is published with open access at Springerlink.com
Abstract Nuclear receptors (NRs) are ligand dependent
transcriptional factors and play a key role in reproduction,
development, and homeostasis of organism. NRs are
potential targets for treatment of cancer and other diseases
such as inflammatory diseases, and diabetes. In this study,
we present a comprehensive library of pocket conforma-
tional ensembles of thirteen human nuclear receptors
(NRs), and test the ability of these ensembles to recognize
their ligands in virtual screening, as well as predict their
binding geometry, functional type, and relative binding
affinity. 157 known NR modulators and 66 structures were
used as a benchmark. Our pocket ensemble library cor-
rectly predicted the ligand binding poses in 94% of the
cases. The models were also highly selective for the active
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