Dynamic behavior of fully solvated beta2-adrenergic receptor, embedded in the membrane with bound agonist or antagonist.

ABSTRACT: Recently we predicted the 3D structure of the human beta2-adrenergic receptor (beta2AR) and of the binding site of several agonists and antagonists to beta2AR. These predictions (MembStruk and HierDock) included no explicit water and only a few lipid molecules. Here we include explicit H(2)O and an infinite lipid bilayer membrane in molecular dynamics (MD) simulations of three systems: apo-beta2AR, epinephrine-bound beta2AR, and butoxamine-bound beta2AR (epinephrine is an endogenous agonist, and butoxamine is a beta2AR selective antagonist). The predicted structures for apo-beta2AR and butoxamine-beta2AR are stable in MD, but in epinephrine-beta2AR, extracellular water trickles into the binding pocket to mediate hydrogen bonding between the catechol of epinephrine and Ser-204 on helix 5. T

SUBMITTER: Spijker P 

PROVIDER: S-EPMC1458764 | biostudies-literature | 2006 Mar

REPOSITORIES: biostudies-literature