Studies On The Interactions Among Transmembrane Domains Of Membrane Protein With Molecular Dynamics Simulation

CD36, GP, DAP12were well researched in our lab, they aremultifunctional and play a vital role on the cell membrane. Our group has usedvarious biochemistry methods to study their transmembrane(TM) domaininteractions. We found that their TM domains could self-assemble intooligomerization and regulate signaling transmission. We used to study deeplyon how these TM domains interact with each other in the bilayer and integrateinto oligomer by molecular dynamics simulation.First, atomatics simulation(AT-MD) was applied to study the features ofCD36TM1WT and its mutant G16I. We found that G8has little effect andG12has small effect on dimerizaton. G16, A20, G23pairs have stronginteraction driving the2TM helices into dimer. When G16was mutate into I,the2TM helice could not self-assemble into dimer.Second, AT-MD was used to study the packing course of the GPIB-IXcomplex and found that several polar residues have dominant role in complexoligomerization. These residues are Y492, A502, S503of IB, Q129, H139ofIBβ, D135and some hydrophobic residues of IX. Finally, coarse-grained simulation(CG-MD) was utilized to study DAP12.V42WT generate a bimodal packing dimer in crossing angle distribution, andthe left-handed(LH) packing had higher peek than right-handed(RH), LH andRH packing both shared same concentrated helix spatial contact area. Inadditional, LH packing was more stable dimer proved by the following AT-MD. All the non-disruptive mutants had similar crossing angle distributionsand helix spatial contacts with V42WT. In contrast, all the disruptive mutantscould not form stable dimmers and had fewer LH paking dimers than V42, andshow scattered helix spatial contacts area.Overall,2kinds of molecular dynamics simulation method (AT-MD andCG-MD) were used to research TM domain interactions. The simulation datasverified the biochemical test results and explained the interaction mechanismsat the amino acid molecular level. Moreover, the datas could forecast somenew TM peptide interaction sites and guide future biochemical experiments.