Theoretical evidence of a salt bridge disruption as the initiating process for the α1d-adrenergic receptor activation:: a molecular dynamics and docking study

This study reports the building of the three-dimensional structure of the rat a,,adrenergic receptor through a topology approach based on the structure of the rhodopsin receptor from cryoelectron microscopy. The validity and reliability of the receptor model were assessed through exhaustive molecular dynamics and docking studies. Some interesting ligand-receptor interactions were identified along with significant differences between the binding mode of agonists and antagonists. The importance of the disruption of a salt bridge as a possible initial event leading to receptor activation is discussed on the basis of data from mutagenesis and molecular dynamics studies. Proteins 2001;43:382-394. (C) 2001 Wiley-Liss, Inc.