Theoretical evidence of a salt bridge disruption as the initiating processfor the alpha(1d)-adrenergic receptor activation: a molecular dynamics anddocking study

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