02159nas a2200205   4500008004100000020004100041022001400082245006900096210006800165260009100233300001200324490000800336520140300344100002001747700001801767700002601785700002801811700001501839856009901854       2016                        eng d  a978-0-12-803612-9; 978-0-12-803595-5  a0091-679X00aWhat can simulations tell us about GPCRs: integrating the scales0 aWhat can simulations tell us about GPCRs integrating the scales  a525 B Street, Suite 1900, San Diego, CA 92101-4495 USA :bElsevier Academic Press Inc.  a429-4520 v1323 a<p>The functional dynamics of G protein-coupled receptors (GPCRs) encompasses multiple spatiotemporal scales, ranging from femtoseconds to seconds and Angstroms to micrometers. Computational approaches, often in close collaboration with experimental methods, have been invaluable in unraveling GPCR structure and dynamics at these various hierarchical levels. The binding of natural and synthetic ligands to the wild-type and naturally occurring variant receptors have been analyzed by several computational methods. The activation of receptors from the inactive to the active state has been investigated by atomistic simulations and ongoing work on several receptors will help uncover general and receptor-specific mechanisms. The interaction of GPCRs with complex membranes that contain phospholipids and cholesterol have been probed by coarse-grain methods and shown to directly influence receptor association. In this chapter, we discuss computational approaches that have been successful in analyzing each scale of GPCR dynamics. An overview of these approaches will allow a more judicious choice of the appropriate method. We hope that an appreciation of the power of current computational approaches will encourage more critical collaborations. A comprehensive integration of the different approaches over the entire spatiotemporal scales promises to unravel new facets of GPCR function.</p>1 aSengupta, Durba1 aJoshi, Manali1 aAthale, Chaitanya, A.1 aChattopadhyay, Amitabha1 aShukla, AK  uhttps://library.ncl.res.in/content/what-can-simulations-tell-us-about-gpcrs-integrating-scales00660nas a2200181   4500008004100000022001400041245009900055210006900154260000800223300000800231490000700239100002500246700001900271700001900290700002000309700001800329856013100347       2021                        eng d  a0175-757100aWater mediated allosteric network in beta 2AR T164I variant modulates agonist binding affinity0 aWater mediated allosteric network in beta 2AR T164I variant modu  cJUL  a1620 v501 aNikte, Siddhanta, V.1 aSonar, Krushna1 aTandale, Aditi1 aSengupta, Durba1 aJoshi, Manali  uhttps://library.ncl.res.in/content/water-mediated-allosteric-network-beta-2ar-t164i-variant-modulates-agonist-binding-affinity01658nas a2200169   4500008004100000245010500041210006900146260000800215300001100223490000700234520104200241100002001283700002401303700002001327700002001347856012101367       2023                        eng d00aWavelet coherence phase analysis decodes the universal switching mechanism of Ras GTPase superfamily0 aWavelet coherence phase analysis decodes the universal switching  cJUL  a1070310 v263 a<p>
	The Ras superfamily of GTPases regulate critical cellular processes by shuttling between GTP-bound ON and GDP-bound OFF states. This switching mechanism is attributed to the conformational changes in two loops, SWI and SWII, upon GTP binding and hydrolysis. Since these conformational changes vary across the Ras superfamily, there is no generic parameter to define their functional states. A unique wavelet coherence (WC) analysis-based approach developed here shows that the structural changes in switch regions could be mapped onto the wavelet coherence phase couplings (WPCs). Thus, WPCs could serve as unique parameters to define their functional states. Disentanglement of WPCs in oncogenic GTPases shows how breakdown of structural allostery leads to their aberrant function. These observations stand out even for simulated ensemble of switch region conformers. Overall, for the first time, we show that WPCs could unravel the latent structural deviations in Ras proteins to decode their universal switching mechanism.</p>
1 aMotiwala, Zenia1 aSandholu, Anand, S.1 aSengupta, Durba1 aKulkarni, Kiran  uhttps://library.ncl.res.in/content/wavelet-coherence-phase-analysis-decodes-universal-switching-mechanism-ras-gtpase