02060nas a2200169   4500008004100000020001800041245011900059210006900178260000800247300001200255490000800267520142900275100001801704700002101722700002001743856012701763       2022                        eng d  a978032398895700aMolecular determinants of GPCR pharmacogenetics: deconstructing the population variants in β2-adrenergic receptor0 aMolecular determinants of GPCR pharmacogenetics deconstructing t  cJAN  a361-3960 v1283 a<p>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. In this chapter, we provide an overview on GPCR structure and activation, with a special focus on the β2-adrenergic receptor (β2-AR). First, we discuss the current understanding of the structural and dynamic features of the wildtype receptor. Subsequently, the population variants identified in this receptor from clinical and large-scale genomic studies are described. We show how computational approaches such as bioinformatics tools and molecular dynamics simulations can be used to characterize the variant receptors in comparison to the wildtype receptor. In particular, we discuss three examples of clinically important variants and discuss how the structure and function of these variants differ from the wildtype receptor at a molecular level. Overall, the chapter provides an overview of structure and function of GPCR variants and is a step towards the study of inter-individual differences and personalized medicine.</p>
1 aJoshi, Manali1 aNikte, Siddhanta1 aSengupta, Durba  uhttps://library.ncl.res.in/content/molecular-determinants-gpcr-pharmacogenetics-deconstructing-population-variants-%CE%B22