02001nas a2200205   4500008004100000022001400041245008200055210006900137260011000206300001400316490000700330520119600337100002401533700002501557700002501582700002601607700002601633700002001659856011601679       2015                        eng d  a1463-907600aThermodynamic and kinetic characterization of transmembrane helix association0 aThermodynamic and kinetic characterization of transmembrane heli  aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcNOV  a1390-13980 v173 a<p>The transient dimerization of transmembrane proteins is an important event in several cellular processes and computational methods are being increasingly used to quantify their underlying energetics. Here, we probe the thermodynamics and kinetics of a simple transmembrane dimer to understand membrane protein association. A multi-step framework has been developed in which the dimerization profiles are calculated from coarse-grain molecular dynamics simulations, followed by meso-scale simulations using parameters calculated from the coarse-grain model. The calculated value of Delta G(assoc) is approx. -20 kJ mol(-1) and is consistent between three methods. Interestingly, the meso-scale stochastic model reveals low dimer percentages at physiologically-relevant concentrations, despite a favorable Delta G(assoc). We identify generic driving forces arising from the protein backbone and lipid bilayer and complementary factors, such as protein density, that govern self-interactions in membranes. Our results provide an important contribution in understanding membrane protein organization and linking molecular, nano-scale computational studies to meso-scale experimental data.</p>1 aPawar, Aiswarya, B.1 aDeshpande, Sneha, A.1 aGopal, Srinivasa, M.1 aWassenaar, Tsjerk, A.1 aAthale, Chaitanya, A.1 aSengupta, Durba  uhttps://library.ncl.res.in/content/thermodynamic-and-kinetic-characterization-transmembrane-helix-association-002400nas a2200181   4500008004100000245010500041210006900146260000800215300001100223490000900234520173200243100002501975700002402000700001702024700002602041700002002067856013102087       2017                        eng d00aRole of spatial inhomogenity in GPCR dimerisation predicted by receptor association-diffusion models0 aRole of spatial inhomogenity in GPCR dimerisation predicted by r  cJUN  a0360020 v14  3 aG protein-coupled receptor (GPCR) association is an emerging paradigm with far reaching implications in the regulation of signalling pathways and therapeutic interventions. Recent super resolution microscopy studies have revealed that receptor dimer steady state exhibits sub-second dynamics. In particular the GPCRs, muscarinic acetylcholine receptor M-1 (M1MR) and formyl peptide receptor (FPR), have been demonstrated to exhibit a fast association/dissociation kinetics, independent of ligand binding. In this work, we have developed a spatial kinetic Monte Carlo model to investigate receptor homo-dimerisation at a single receptor resolution. Experimentally measured association/dissociation kinetic parameters and diffusion coefficients were used as inputs to the model. To test the effect of membrane spatial heterogeneity on the simulated steady state, simulations were compared to experimental statistics of dimerisation. In the simplest case the receptors are assumed to be diffusing in a spatially homogeneous environment, while spatial heterogeneity is modelled to result from crowding, membrane micro-domains and cytoskeletal compartmentalisation or 'corrals'. We show that a simple association-diffusion model is sufficient to reproduce M1MR association statistics, but fails to reproduce FPR statistics despite comparable kinetic constants. A parameter sensitivity analysis is required to reproduce the association statistics of FPR. The model reveals the complex interplay between cytoskeletal components and their influence on receptor association kinetics within the features of the membrane landscape. These results constitute an important step towards understanding the factors modulating GPCR organisation.1 aDeshpande, Sneha, A.1 aPawar, Aiswarya, B.1 aDighe, Anish1 aAthale, Chaitanya, A.1 aSengupta, Durba  uhttps://library.ncl.res.in/content/role-spatial-inhomogenity-gpcr-dimerisation-predicted-receptor-association-diffusion-models