@article { ISI:000358627400006,
	title = {Molecular dynamics simulations of GPCR-cholesterol interaction: an emerging paradigm},
	journal = {Biochimica Et Biophysica Acta-Biomembranes},
	volume = {1848},
	number = {9, SI},
	year = {2015},
	month = {SEP},
	pages = {1775-1782},
	publisher = {ELSEVIER SCIENCE BV},
	address = {PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS},
	abstract = {<p>G protein-coupled receptors (GPCRs) are the largest class of molecules involved in signal transduction across cell membranes and represent major targets in the development of novel drug candidates. Membrane cholesterol plays an important role in GPCR structure and function. Molecular dynamics simulations have been successful in exploring the effect of cholesterol on the receptor and a general consensus molecular view is emerging. We review here recent molecular dynamics studies at multiple resolutions highlighting the main features of cholesterol-GPCR interaction. Several cholesterol interaction sites have been identified on the receptor that are reminiscent of nonannular sites. These cholesterol hot-spots are highly dynamic and have a microsecond time scale of exchange with the bulk lipids. A few consensus sites (such as the CRAC site) have been identified that correspond to higher cholesterol interaction. Interestingly, high plasticity is observed in the modes of cholesterol interaction and several sites have been suggested to have high cholesterol occupancy. We therefore believe that these cholesterol hot-spots are indicative of {\textquoteleft}high occupancy sites{\textquoteright} rather than {\textquoteleft}binding sites{\textquoteright}. The results suggest that the energy landscape of cholesterol association with GPCRs corresponds to a series of shallow minima interconnected by low barriers. These specific interactions, along with general membrane effects, have been observed to modulate GPCR organization. Membrane cholesterol effects on receptor structure and organization, that in turn influences receptor cross-talk and drug efficacy, represent a new frontier in GPCR research. This article is part of a Special Issue entitled: Lipid-protein interactions. Guest Editors: Amitabha Chattopadhyay and jean-Marie Ruysschaert. (C) 2015 Elsevier B.V. All rights reserved.</p>},
	keywords = {Coarse-grain simulation, CRAC, GPCR, Lipid-receptor interaction, Membrane cholesterol, Receptor dimerization},
	issn = {0005-2736},
	doi = {10.1016/j.bbamem.2015.03.018},
	author = {Sengupta, Durba and Chattopadhyay, Amitabha}
}
@article {44521,
	title = {Membrane-induced organization and dynamics of the N-terminal domain of chemokine receptor CXCR1: insights from atomistic simulations},
	journal = {Chemistry and Physics of Lipids},
	volume = {210},
	year = {2018},
	month = {JAN},
	pages = {142-148},
	abstract = {<p>The CXC chemokine receptor 1 (CXCR1) is an important member of the G protein-coupled receptor (GPCR) family in which the extracellular N-terminal domain has been implicated in ligand binding and selectivity. The structure of this domain has not yet been elucidated due to its inherent dynamics, but experimental evidence points toward membrane-dependent organization and dynamics. To gain molecular insight into the interaction of the N-terminal domain with the membrane bilayer, we performed a series of microsecond time scale atomistic simulations of the N-terminal domain of CXCR1 in the presence and absence of POPC bilayers. Our results show that the peptide displays a high propensity to adopt a beta-sheet conformation in the presence of the membrane bilayer. The interaction of the peptide with the membrane bilayer was found to be transient in our simulations. Interestingly, a scrambled peptide, containing the same residues in a randomly varying sequence, did not exhibit membrane-modulated structural dynamics. These results suggest that sequence-dependent electrostatics, modulated by the membrane, could play an important role in folding of the N-terminal domain. We believe that our results reinforce the emerging paradigm that cellular membranes could be important modulators of function of G protein-coupled receptors such as CXCR1.</p>},
	keywords = {All atom MD simulations, beta-sheet, CXCR1, Membrane interaction, N-terminal},
	issn = {0009-3084},
	doi = {10.1016/j.chemphyslip.2017.09.003},
	author = {Kharche, Shalmali and Joshi, Manali and Sengupta, Durba and Chattopadhyay, Amitabha}
}
@inbook {47149,
	title = {Molecular determinants of GPCR oligomerization},
	booktitle = {Molecular determinants of GPCR oligomerization},
	number = {GPCRs},
	year = {2020},
	pages = {97-108},
	doi = {10.1016/B978-0-12-816228-6.00006-4},
	author = {Mohole, Madhura and Kumar, G. Aditya and Sengupta, Durba and Chattopadhyay, Amitabha}
}
