Characterization of ligand type of estrogen receptor by MD simulation and mm-PBSA free energy analysis.

ABSTRACT: Estrogen receptor is a transcription regulator and can bind structurally distinct ligands with full agonistic, SERMs, or full antagonistic properties. Crystal structures of the ER ligand binding domain (LBD)-complexed with full agonists or SERMs show that these ligands induce two different orientations of Helix12 in LBD and generate two different conformations, agonist conformation (A conformation) and AF2 antagonist conformation (B conformation). To understand how ER ligands interact with LBD structurally and energetically, we docked 3 full agonists, 9 SERMs and 2 full antagonists in both the A and B conformation of ERα LBD and performed a 4-step molecular dynamics (MD) simulation on all 28 complexes followed by mm-PBSA binding free energy calculation. We found that all full agonists pref

SUBMITTER: Liu JY 

PROVIDER: S-EPMC3180098 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature