@article { ISI:000362849600271,
	title = {Landscapes of membrane protein interactions from high-throughput MD simulations using the daft approach},
	journal = {Biophysical Journal},
	volume = {108},
	number = {2, 1},
	year = {2015},
	note = {59th Annual Meeting of the Biophysical-Society, Baltimore, MD, FEB 07-11, 2015},
	month = {JAN},
	pages = {526A-526A},
	publisher = {Biophys Soc},
	address = {600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA},
	issn = {0006-3495},
	author = {Wassenaar, Tsjerk A. and Pluhackova, Kristyna and Moussatova, Anastassiia and Sengupta, Durba and Marrink, Siewert-Jan and Tieleman, D. Peter and Boeckmann, Rainer A.}
}
@article {46757,
	title = {Lipid-dependent conformational landscape of the ErbB2 growth factor receptor dimers},
	journal = {Chemistry and Physics of Lipids},
	volume = {230},
	year = {2020},
	month = {AUG},
	pages = {104911},
	type = {Article},
	abstract = {<p>Altered lipid metabolism has been linked to cancer development and progression. Several roles have been attributed to the increased saturation and length of lipid acyl tails observed in tumors, but its effect on signaling receptors is still emerging. In this work, we have analyzed the lipid dependence of the ErbB2 growth factor receptor dimerization that plays an important role in the pathogenesis of breast cancer. We have performed coarse-grain ensemble molecular dynamics simulations to comprehensively sample the ErbB2 monomer-dimer association. Our results indicate a dynamic dimer state with a complex conformational landscape that is modulated with increasing lipid tail length. We resolve the native N-terminal {\textquoteleft}{\textquoteleft}active{\textquoteright}{\textquoteright} and C-terminal {\textquoteleft}{\textquoteleft}inactive{\textquoteright}{\textquoteright} conformations in all membrane compositions. However, the relative population of the N-terminal and C-terminal conformers is dependent on length of the saturated lipid tails. In short-tail membranes, additional non-specific dimers are observed which are reduced or absent in long-tailed bilayers. Our results indicate that the relative population as well as the structure of the dimer state is modulated by membrane composition. We have correlated these differences to local perturbations of the membrane around the receptor. Our work is an important step in characterizing ErbB dimers in healthy and diseased states and emphasize the importance of sampling lipid dynamics in understanding receptor association.</p>
},
	keywords = {ErbB2 dimer, Lipid effects, Martini coarse-grained simulations, Membrane protein structure, Transmembrane association},
	issn = {0009-3084},
	doi = {10.1016/j.chemphyslip.2020.104911},
	author = {Gopal, Srinivasa M. and Pawar, Aiswarya B. and Wassenaar, Tsjerk A. and Sengupta, Durba}
}
@article {47034,
	title = {Loss of a water-mediated network results in reduced agonist affinity in a beta(2)-adrenergic receptor clinical variant},
	journal = {Biochimica ET Biophysica Acta-Proteins and Proteomics},
	volume = {1869},
	year = {2021},
	month = {APR},
	pages = {140605},
	type = {Article},
	abstract = {<p>The beta(2)-adrenergic receptor (beta(2)AR) 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 {\textquoteleft}{\textquoteleft}non-deleterious{\textquoteright}{\textquoteright} 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. We are able to identify hydration sites in the transmembrane domain that are essential to maintain the integrity of the binding site but are absent in the variant. The loss of these hydration sites in the variant correlates with perturbations in the intra-protein interaction network and rearrangements in the orthosteric ligand binding site. In conjunction, we observe an altered binding and reduced free energy of a series of agonists, in line with experimental trends. Our work identifies a functional allosteric pathway connected by specific hydration sites in beta(2)AR that has not been reported before and provides insight into water-mediated networks in GPCRs in general. Overall, the work is one of the first step towards developing variant-specific potent and selective agonists.</p>
},
	keywords = {beta(2)-Adrenergic receptor, G protein coupled receptor, GPCR, molecular dynamics, Pharmacogenetics, SNP},
	issn = {1570-9639},
	doi = {10.1016/j.bbapap.2021.140605},
	author = {Nikte, V. Siddhanta and Sonar, Krushna and Tandale, Aditi and Joshi, Manali and Sengupta, Durba}
}
