01891nas a2200169   4500008004100000022001400041245010900055210006900164260011000233300001600343490000700359520116300366100002101529700002001550700002001570856013101590       2013                        eng d  a1463-907600aSequence dependent lipid-mediated effects modulate the dimerization of ErbB2 and its associative mutants0 aSequence dependent lipidmediated effects modulate the dimerizati  aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcSEP  a19031-190410 v153 a<p>The association of transmembrane helices is an important event in several biological processes, but the factors governing association, especially the non-specific environmental effects, have still not been elucidated. Here, we use coarse-grain molecular dynamics simulations to study the association of ErbB2 transmembrane helices and three ``oncogenic mutants.'' Self-assembly simulations and the dimerization free-energy profiles confirm an energetically-favorable dimerized state for both the wildtype and the mutants. The dissociation free energy of all three mutants is calculated to be larger than the wildtype peptide. Along with favourable protein-protein interactions, non-specific environmental effects are observed to contribute to the association. In particular, local bilayer thinning along with membrane perturbations are seen around the mutants. The membrane perturbations are reduced upon helix association, suggesting that lipid chain packing is an important driving force for helix dimerization. Our results highlight the importance of both specific as well as non-specific driving forces in the association of transmembrane helices.</p>1 aPrasanna, Xavier1 aPraveen, P., J.1 aSengupta, Durba  uhttps://library.ncl.res.in/content/sequence-dependent-lipid-mediated-effects-modulate-dimerization-erbb2-and-its-associative-0