Improved docking, screening and selectivity prediction for small molecule nuclear receptor modulators using conformational ensembles.

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 conformational 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 correctly predicted the ligand binding poses in 94% of the cases. The models were also highly selective for the active ligands in virt

SUBMITTER: Park SJ 

PROVIDER: S-EPMC2881208 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature