02081nas a2200241   4500008004100000022001400041245008800055210006900143260000800212300001100220490000800231520127200239653002801511653002101539653002501560653003501585653002701620100002001647700001901667700002001686700002801706856010501734       2024                        eng d  a0301-462200aProbing the energy landscape of the lipid interactions of the serotonin 1A receptor0 aProbing the energy landscape of the lipid interactions of the se  cOCT  a1072890 v3133 a<p>
	G protein-coupled receptors (GPCRs) are lipid-regulated transmembrane proteins that play a central role in cell signaling and pharmacology. Although the role of membrane lipids in GPCR function is well established, the underlying GPCR-lipid interactions have not been thermodynamically characterized due to the complexity of these interactions. In this work, we estimate the energetics and dynamics of lipid association from coarse-grain simulations of the serotonin1A receptor embedded in a complex membrane. We show that lipids bind to the receptor with varying energetics of 1-4 kT, and timescales of 1-10 mu s. The most favorable energetics and longest residence times are observed for cholesterol, glycosphingolipid GM1, phosphatidylethanolamine (PE) and phosphatidylserine (PS) lipids. Multi-exponential fitting of the contact probability suggests distinct dynamic regimes, corresponding to ps, ns and mu s timescales, that we correlate with the annular, intermediate and nonannular lipid sites. The timescales of lipid binding correspond to high barrier heights, despite their relatively weaker energetics. Our results highlight that GPCR-lipid interactions are driven by both thermodynamic interactions and the dynamical features of lipid binding.</p>
10aGPCR-lipid interactions10aLipid energetics10aLipid residence time10aMolecular dynamics simulations10aSerotonin 1 a receptor1 aMohole, Madhura1 aNaglekar, Amit1 aSengupta, Durba1 aChattopadhyay, Amitabha  uhttps://library.ncl.res.in/content/probing-energy-landscape-lipid-interactions-serotonin-1a-receptor