State-dependent dynamics of extramembrane domains in the β -adrenergic receptor.

G protein-coupled receptors (GPCRs) are membrane-bound signaling proteins that play an essential role in cellular signaling processes. Due to their intrinsic function of transmitting internal signals in response to external cues, these receptors are adapted to be highly dynamic in nature. The β -adrenergic receptor (β AR) is a representative member of the family that has been extensively analyzed in terms of its structure and activation.

Molecular determinants of GPCR pharmacogenetics: Deconstructing the population variants in β-adrenergic receptor.

G protein-coupled receptors (GPCRs) are membrane proteins that play a central role in cell signaling and constitute one of the largest classes of drug targets. The molecular mechanisms underlying GPCR function have been characterized by several experimental and computational methods and provide an understanding of their role in physiology and disease. Population variants arising from nsSNPs affect the native function of GPCRs and have been implicated in differential drug response.

Molecular Characterization of the β-like Octopamine Receptor of Helicoverpa armigera.

Helicoverpa armigera is a devastating polyphagous and cosmopolitan crop pest. There are reports of this insect being resistant to a variety of pesticides raising concern worldwide. The Octopamine (OA) binding β-like receptor (OAR), a GPCR, is widely distributed in the nervous system of the insect and plays essential roles in the physiology and development and thus is an important target for insecticides.

Loss of a water-mediated network results in reduced agonist affinity in a β-adrenergic receptor clinical variant.

The β-adrenergic receptor (βAR) is a member of the G protein-coupled receptor (GPCR) family that is an important drug target for asthma and COPD. Clinical studies coupled with biochemical data have identified a critical receptor variant, Thr164Ile, to have a reduced response to agonist-based therapy, although the molecular mechanism underlying this seemingly "non-deleterious" substitution is not clear. Here, we couple molecular dynamics simulations with network analysis and free-energy calculations to identify the molecular determinants underlying the differential drug response.

Differential Dynamics Underlying the Gln27Glu Population Variant of the β-Adrenergic Receptor.

The β-adrenergic receptor (βAR) is a membrane-bound G-protein-coupled receptor and an important drug target for asthma. Clinical studies report that the population variant Gln27Glu is associated with a differential response to common asthma drugs, such as albuterol, isoproterenol and terbutaline. Interestingly, the 27th amino acid is positioned on the N-terminal region that is the most flexible and consequently the least studied part of the receptor.