The juxtamembrane (JM) domain of the EGFR is crucial for receptor activation and also plays an important role in regulation of the kinase domain (Hubbard, 2004). The JM region starts immediately after the TM domain, at residue Arg645, referred to as JM-A (residues 645-663) and JM-B (residues 664-682). It is suggested that the JM-A region forms an antiparallel dimer and interacts with negatively charged lipids in the adjacent lipid bilayer. However its precise orientation and involvement in the activation mechanism is not clearly understood.In this study, we employ coarse grained molecular dynamics (CG-MD) simulations to investigate the behaviour of the EGFR TM-JM domain dimer in various membrane environments. Our simulations reveal that the JM region interacts favourably with charged lipids, and in particular forms a high number of contacts between positively charged residues in the JM-A and anionic lipid headgroups. The resulting CG models were refined further using atomistic simulations. We have also extended this study to investigate the behavior of the juxtamembrane region in the presence of extracellular and kinase domain in order to gain more insights into the orientation of the JM region and its possible involvement in EGFR activation mechanism.S.R. Hubbard, “Juxtamembrane autoinhibition in receptor tyrosine kinases.,” Nature reviews. Molecular cell biology, vol. 5, Jun. 2004, pp. 464-71.