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APS March Meeting

MOLECULAR DYNAMICS SIMULATION STUDY OF MULTIMERIZATION OF THE MMS6 PROTEIN FROM MAGNETOSPIRILLUM MAGNETICUM STRAIN AMB-1. Monica H. Lamm 2 , Rastko Sknepnek 1 , Lijun Wang 3 , Marit Nilsen-Hamilton 3. 1 Department of Physics and Astronomy

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APS March Meeting

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  1. MOLECULAR DYNAMICS SIMULATION STUDY OF MULTIMERIZATION OF THE MMS6 PROTEIN FROM MAGNETOSPIRILLUM MAGNETICUM STRAIN AMB-1 Monica H. Lamm2, Rastko Sknepnek1, Lijun Wang3, Marit Nilsen-Hamilton3 1Department of Physics and Astronomy 2Department of Chemical and Biological Engineering 3Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University and DOE Ames Laboratory APS March Meeting March 17, 2009 1/12

  2. Motivation Magnetotactic bacteria - Magnetospirillummagneticum AMB-1 • main structure of interest are magnetosomes: • vesicles containing magnetite (Fe3O4) nanocrystals • nanocrystals ~50nm in length • form a long linear chain 1. Understand formation of magnetite nanocrystals. 2. Mimic it in the laboratory. 3. Control the self-assembly by organic (block copolymer) matrix. Talk Y14.00007 Study Mms6 protein which appears to be crucial for nanocrystals formation 500nm Bearth (from T. Prozorov, et al. ACS Nano1, 228 (2007)) APS March Meeting March 17, 2009 2/12

  3. Experiments on bacteria show presence of Mms6 protein is in magnetosomes. (Arakakiet al., J. Biol. Chem., 278, 8745 (2003)) Experiments with Pluronic® copolymers: Mms6 is crucial for growth of magnetite nanocrystals. (T. Prozorov, et al. ACS Nano1, 228 (2007)) Mms6 protein Structure is at present not known. • Short protein: • sequence: GGTIWTGKGLGLGLGLGLGAWGPIILGVVGAGAVYAYMKSRDIESAQSDEEVELRDALA • 59 amino acids • molecular weight: 5961 g/mol • approximate diameter: 2.5 nm hydrophobic N-terminus C21-terminus hydrophilic C25-terminus Mms6 aggregates in a solution. Is this a membrane protein? APS March Meeting March 17, 2009 3/12

  4. Modeling Aggregation and interaction with a phospholipid bilayer. Atomistic simulations are not feasible: • multimers contain tens of proteins • relevant time scales are hundreds of nanoseconds • protein structure is at present not known Use an intermediate level coarse grained model. APS March Meeting March 17, 2009 4/12

  5. Coarse-grained model Protein DPPC phospholipid L0 Model by Marrink et al. JPC-B 108, 750 (2004). Model by Shih, et al. J. Phys. Chem B 110, 3674 (2006). water APS March Meeting March 17, 2009 5/12

  6. Bonded interactions Harmonic bond: Angle interaction: Nonbonded interactions Dihedral interaction: APS March Meeting March 17, 2009 6/12

  7. Molecular dynamics Simulations performed with LAMMPS (S. Plimpton, J. Comp. Phys. 117, 1 (1995); lammps.sandia.gov) Initial configurations build by CGBuilder Python toolkit. APS March Meeting March 17, 2009 7/12

  8. Results -single chain studies Mms6 after 300 ns C21 terminus after 300 ns (KSRDIESAQSDEEVELRDALA) GGTIWTGKGLGLGLGLGLGAWGPIILGVVGAGAV YAYMKSRDIESAQSDEEVELRDALA negative polar positive nonpolar/apolar APS March Meeting March 17, 2009 8/12

  9. Results -multimerization studies Two multimers of sizes 13 and 16! 30 C21 chains in a L=150A box after 170ns (water molecules not shown) negative polar positive nonpolar/apolar APS March Meeting March 17, 2009 9/12

  10. One large aggregate! 30 Mms6 chains in a L=130A box after 175ns (water molecules not shown) negative polar positive nonpolar/apolar APS March Meeting March 17, 2009 10/12

  11. Results – Mms6 in a DPPC bilayer (water not shown) Starting from a random configuration, bilayer with embedded proteins froms within approximately 60ns. Mms6 is likely to be a membrane protein negative polar 10 Mms6 proteins and 1024 DPPC molecules after 180ns. positive nonpolar/apolar APS March Meeting March 17, 2009 11/12

  12. Summary and Conclusions Mms6 protein: • small protein present in magnetosomes of magnetotactic bacteria • plays major role in growth of magnetite nanocrystals • forms multimers in a solution We have used an intermediate level coarse grained model to simulate assembly of multimers and interaction with a phospholipid bilayer. Coarse grained model qualitatively agrees with experiments. Our simulation suggest that Mms6 is a membrane protein. Recent experiments suggest that Mms6 binds iron III. Our model needs improvement to explain this phenomenon. APS March Meeting March 17, 2009 12/12

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