Nanorobotics pp 425-455 | Cite as

Protein-Based Nanoscale Actuation

  • Gaurav Sharma
  • Atul Dubey
  • Constantinos Mavroidis


This chapter discusses protein-based nanoscale actuation mechanisms with two illustrative examples, the viral protein linear nanoActuator and the GCN4 peptide nanoActuator. The VPL peptide is based on the conformation change mechanism of envelope glycoprotein of naturally occurring retroviruses. The GCN4 is an artificial design based on two α-helical coils. Structural features, stability, and optimal design considerations are described in detail. Computational methods are applied to gain knowledge about a given molecule and its suitability to function as a nanoActuator.


Protein Data Bank Root Mean Square Deviation Coiled Coil Fusion Peptide Steer Molecular Dynamic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Mavroidis C, Dubey A (2003) Biomimetics: from pulses to motors. Nat Mater 2(9):573–574CrossRefGoogle Scholar
  2. 2.
    Mavroidis C, Dubey A, Yarmush ML (2004) Molecular machines. Annu Rev Biomed Eng 6(1):363–395. doi: 10.1146/annurev.bioeng.6.040803.140143 CrossRefGoogle Scholar
  3. 3.
    Sharma G, Badescu M, Dubey A, Mavroidis C, Tomassone SM, Yarmush ML (2005) Kinematics and workspace analysis of protein based nano-actuators. J Mech Des 127(4): 718–727. doi: 10.1115/1.1900751 CrossRefGoogle Scholar
  4. 4.
    Boyer PD (1998) Energy, life, and ATP. Biosci Rep 18(3):97–117CrossRefGoogle Scholar
  5. 5.
    Oster G, Wang H (2003) Rotary protein motors. Trends Cell Biol 13(3):114–121CrossRefGoogle Scholar
  6. 6.
    Vale RD, Milligan RA (2000) The way things move: looking under the hood of molecular motor proteins. Science 288(5463):88–95CrossRefGoogle Scholar
  7. 7.
    Berg HC (2003) The rotary motor of bacterial flagella. Annu Rev Biochem 72:19–54CrossRefGoogle Scholar
  8. 8.
    Seeman NC (2003) DNA in a material world. Nature 421(6921):427–431MathSciNetCrossRefGoogle Scholar
  9. 9.
    Yurke B, Turberfield AJ, Mills AP, Simmel FC, Neumann JL (2000) A DNA-fuelled molecular machine made of DNA. Nature 415:62–65Google Scholar
  10. 10.
    Balzani VV, Credi A, Raymo FM, Stoddart JF (2000) Artificial molecular machines. Angew Chem Int Ed Engl 39(19):3348–3391CrossRefGoogle Scholar
  11. 11.
    Dubey A, Mavroidis C, Thornton A, Nikitczuk K, Yarmush ML (2003) Viral protein linear (VPL) nano-actuators. In: 2003 Third IEEE conference on nanotechnology, 2003 (IEEE-NANO 2003), 12–14 Aug 2003, vol 142. pp 140–143Google Scholar
  12. 12.
    Skehel JJ, Wiley DC (2000) Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 69:531–569CrossRefGoogle Scholar
  13. 13.
    Wiley DC, Skehel JJ (1987) The structure and function of the hemagglutinin membrane glycoprotein of influenza virus. Annu Rev Biochem 56:365–394CrossRefGoogle Scholar
  14. 14.
    Schoch C, Blumenthal R, Clague MJ (1992) A long-lived state for influenza virus-erythrocyte complexes committed to fusion at neutral pH. FEBS Lett 311(3):221–225CrossRefGoogle Scholar
  15. 15.
    Weissenhorn W, Dessen A, Calder LJ, Harrison SC, Skehel JJ, Wiley DC (1999) Structural basis for membrane fusion by enveloped viruses. Mol Membr Biol 16(1):3–9CrossRefGoogle Scholar
  16. 16.
    Lazarowitz SG, Compans RW, Choppin PW (1971) Influenza virus structural and nonstructural proteins in infected cells and their plasma membranes. Virology 46(3):830–843CrossRefGoogle Scholar
  17. 17.
    Skehel JJ, Waterfield MD (1975) Studies on the primary structure of the influenza virus hemagglutinin. Proc Natl Acad Sci USA 72(1):93–97CrossRefGoogle Scholar
  18. 18.
    Wilson IA, Skehel JJ, Wiley DC (1981) Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature 289(5796):366–373CrossRefGoogle Scholar
  19. 19.
    Weis W, Brown JH, Cusack S, Paulson JC, Skehel JJ, Wiley DC (1988) Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid. Nature 333(6172): 426–431CrossRefGoogle Scholar
  20. 20.
    Weis WI, Brunger AT, Skehel JJ, Wiley DC (1990) Refinement of the influenza virus hemagglutinin by simulated annealing. J Mol Biol 212(4):737–761CrossRefGoogle Scholar
  21. 21.
    Bullough PA, Hughson FM, Skehel JJ, Wiley DC (1994) Structure of influenza haemagglutinin at the pH of membrane fusion. Nature 371(6492):37–43CrossRefGoogle Scholar
  22. 22.
    Carr CM, Kim PS (1993) A spring-loaded mechanism for the conformational change of influenza hemagglutinin. Cell 73(4):823–832CrossRefGoogle Scholar
  23. 23.
    Carr CM, Chaudhry C, Kim PS (1997) Influenza hemagglutinin is spring-loaded by a metastable native conformation. Proc Natl Acad Sci USA 94(26):14306–14313CrossRefGoogle Scholar
  24. 24.
    Chan DC, Fass D, Berger JM, Kim PS (1997) Core structure of gp41 from the HIV envelope glycoprotein. Cell 89(2):263–273CrossRefGoogle Scholar
  25. 25.
    Singh M, Berger B, Kim PS (1999) LearnCoil-VMF: computational evidence for coiled-coil-like motifs in many viral membrane-fusion proteins. J Mol Biol 290(5):1031–1041CrossRefGoogle Scholar
  26. 26.
    Caffrey M, Cai M, Kaufman J, Stahl SJ, Wingfield PT, Covell DG, Gronenborn AM, Clore GM (1998) Three-dimensional solution structure of the 44 kDa ectodomain of SIV gp41. EMBO J 17(16):4572–4584CrossRefGoogle Scholar
  27. 27.
    Kobe B, Center RJ, Kemp BE, Poumbourios P (1999) Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain crystallized as a maltose-binding protein chimera reveals structural evolution of retroviral transmembrane proteins. Proc Natl Acad Sci USA 96(8):4319–4324CrossRefGoogle Scholar
  28. 28.
    Baker KA, Dutch RE, Lamb RA, Jardetzky TS (1999) Structural basis for paramyxovirus-mediated membrane fusion. Mol Cell 3(3):309–319CrossRefGoogle Scholar
  29. 29.
    Weissenhorn W, Calder LJ, Wharton SA, Skehel JJ, Wiley DC (1998) The central structural feature of the membrane fusion protein subunit from the Ebola virus glycoprotein is a long triple-stranded coiled coil. Proc Natl Acad Sci USA 95(11):6032–6036CrossRefGoogle Scholar
  30. 30.
    Colman PM, Lawrence MC (2003) The structural biology of type I viral membrane fusion. Nat Rev Mol Cell Biol 4(4):309–319CrossRefGoogle Scholar
  31. 31.
    Walker JE (1998) ATP synthesis by rotary catalysis (Nobel lecture). Angew Chem Int Ed 37:2308–2319CrossRefGoogle Scholar
  32. 32.
    Schlitter J (1994) Targeted molecular dynamics: a new approach for searching pathways of conformational transitions. J Mol Graph 12:84–89CrossRefGoogle Scholar
  33. 33.
    Dubey A, Mavroidis C, Tomassone MS (2006) Molecular dynamic studies of viral-protein based nano-actuators. J Comput Theor Nanosci 3:885CrossRefGoogle Scholar
  34. 34.
    Dubey A, Sharma G, Mavroidis C, Tomassone SM, Nikitczuk K, Yarmush ML (2004) Dynamics and kinematics of viral protein linear nano-actuators for bio-nano robotic systems. In: Proceedings of the 2004 IEEE international conference on robotics and automation, 2004 (ICRA’04), 26 Apr–1 May 2004, vol 1622. pp 1628–1633Google Scholar
  35. 35.
    Dubey A, Sharma G, Mavroidis C, Tomassone MS, Nikitczuk K, Yarmush ML (2004) Computational studies of viral protein nano-actuators. J Comput Theor Nanosci 1:18–28. doi: 10.1166/jctn.2003.003 CrossRefGoogle Scholar
  36. 36.
    Lazaridis T, Karplus M (1999) Effective energy function for proteins in solution. Proteins 35(2):133–152CrossRefGoogle Scholar
  37. 37.
    Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The Protein Data Bank. Nucleic Acids Res 28(1):235–242CrossRefGoogle Scholar
  38. 38.
    Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. J Mol Graph 14(1):33–38, 27–38CrossRefGoogle Scholar
  39. 39.
    Dubey A, Tomassone MS (2009) Viral protein nano-actuators, computational studies of bio-nanomachines. In: Meyers RA (ed) Encyclopedia of complexity and systems science. Springer, New York, pp 9749–9763Google Scholar
  40. 40.
    Ferrara P, Apostolakis J, Caflisch A (2000) Thermodynamics and kinetics of folding of two model peptides investigated by molecular dynamics simulations. J Phys Chem B 104(20):5000–5010CrossRefGoogle Scholar
  41. 41.
    Ruigrok RW, Martin SR, Wharton SA, Skehel JJ, Bayley PM, Wiley DC (1986) Conformational changes in the hemagglutinin of influenza virus which accompany heat-induced fusion of virus with liposomes. Virology 155(2):484–497CrossRefGoogle Scholar
  42. 42.
    Crick FHC (1953) The packing of α-helices: simple coiled-coils. Acta Crystallogr 6: 689–697CrossRefGoogle Scholar
  43. 43.
    Landschulz WH, Johnson PF, McKnight SL (1988) The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science 240(4860):1759–1764CrossRefGoogle Scholar
  44. 44.
    O’Shea EK, Klemm JD, Kim PS, Alber T (1991) X-ray structure of the GCN4 leucine zipper, a two-stranded, parallel coiled coil. Science 254(5031):539–544CrossRefGoogle Scholar
  45. 45.
    Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, Chipot C, Skeel RD, Kalé L, Schulten K (2005) Scalable molecular dynamics with NAMD. J Comput Chem 26(16): 1781–1802CrossRefGoogle Scholar
  46. 46.
    MacKerell AD, Bashford D, Bellott M, Dunbrack RL, Evanseck JD, Field MJ, Fischer S, Gao J, Guo H, Ha S, Joseph-McCarthy D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, Reiher WE, Roux B, Schlenkrich M, Smith JC, Stote R, Straub J, Watanabe M, Wiorkiewicz-Kuczera J, Yin D, Karplus M (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem 102(18): 3586–3616CrossRefGoogle Scholar
  47. 47.
    Sharma G, Rege K, Budil DE, Yarmush ML, Mavroidis C (2008) Reversible pH-controlled DNA-binding peptide nanotweezers: an in-silico study. Int J Nanomedicine 3(4):505–521Google Scholar
  48. 48.
    Sharma G, Rege K, Budil DE, Yarmush ML, Mavroidis C (2009) Biological force measurement in a protein-based nanoactuator. IEEE Trans Nanotechnol 8(6):684–691CrossRefGoogle Scholar
  49. 49.
    Hendsch ZS, Tidor B (1999) Electrostatic interactions in the GCN4 leucine zipper: substantial contributions arise from intramolecular interactions enhanced on binding. Protein Sci 8(7):1381–1392CrossRefGoogle Scholar
  50. 50.
    Kohn WD, Kay CM, Hodges RS (1995) Protein destabilization by electrostatic repulsions in the two-stranded alpha-helical coiled-coil/leucine zipper. Protein Sci 4(2):237–250CrossRefGoogle Scholar
  51. 51.
    Yu Y, Monera OD, Hodges RS, Privalov PL (1996) Investigation of electrostatic interactions in two-stranded coiled-coils through residue shuffling. Biophys Chem 59(3):299–314CrossRefGoogle Scholar
  52. 52.
    Missimer JH, Steinmetz MO, Jahnke W, Winkler FK, van Gunsteren WF, Daura X (2005) Molecular-dynamics simulations of C- and N-terminal peptide derivatives of GCN4-p1 in aqueous solution. Chem Biodivers 2(8):1086–1104CrossRefGoogle Scholar
  53. 53.
    Mohanty D, Kolinski A, Skolnick J (1999) De novo simulations of the folding thermodynamics of the GCN4 leucine zipper. Biophys J 77(1):54–69CrossRefGoogle Scholar
  54. 54.
    Pineiro A, Villa A, Vagt T, Koksch B, Mark AE (2005) A molecular dynamics study of the formation, stability, and oligomerization state of two designed coiled coils: possibilities and limitations. Biophys J 89(6):3701–3713CrossRefGoogle Scholar
  55. 55.
    Nilges M, Brunger AT (1993) Successful prediction of the coiled coil geometry of the GCN4 leucine zipper domain by simulated annealing: comparison to the X-ray structure. Proteins 15(2):133–146CrossRefGoogle Scholar
  56. 56.
    Vieth M, Kolinski A, Brooks CL 3rd, Skolnick J (1994) Prediction of the folding pathways and structure of the GCN4 leucine zipper. J Mol Biol 237(4):361–367CrossRefGoogle Scholar
  57. 57.
    Kosztin I, Bruinsma R, O’Lague P, Schulten K (2002) Mechanical force generation by G proteins. Proc Natl Acad Sci USA 99(6):3575–3580CrossRefGoogle Scholar
  58. 58.
    Yin H, Wang MD, Svoboda K, Landick R, Block SM, Gelles J (1995) Transcription against an applied force. Science 270(5242):1653–1657CrossRefGoogle Scholar
  59. 59.
    Aksimentiev A, Heng JB, Timp G, Schulten K (2004) Microscopic kinetics of DNA translocation through synthetic nanopores. Biophys J 87(3):2086–2097CrossRefGoogle Scholar
  60. 60.
    Gulla SV, Sharma G, Borbat P, Freed JH, Ghimire H, Benedikt MR, Holt NL, Lorigan GA, Rege K, Mavroidis C, Budil DE (2009) Molecular-scale force measurement in a coiled-coil peptide dimer by electron spin resonance. J Am Chem Soc 131(15):5374–5375CrossRefGoogle Scholar
  61. 61.
    Walensky LD, Kung AL, Escher I, Malia TJ, Barbuto S, Wright RD, Wagner G, Verdine GL, Korsmeyer SJ (2004) Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science 305(5689):1466–1470CrossRefGoogle Scholar
  62. 62.
    Futaki S (2005) Membrane-permeable arginine-rich peptides and the translocation mechanisms. Adv Drug Deliv Rev 57(4):547–558CrossRefGoogle Scholar
  63. 63.
    Kawamura KS, Sung M, Bolewska-Pedyczak E, Gariepy J (2006) Probing the impact of valency on the routing of arginine-rich peptides into eukaryotic cells. Biochemistry 45(4):1116–1127CrossRefGoogle Scholar
  64. 64.
    Woolley GA, Jaikaran AS, Berezovski M, Calarco JP, Krylov SN, Smart OS, Kumita JR (2006) Reversible photocontrol of DNA binding by a designed GCN4-bZIP protein. Biochemistry 45(19):6075–6084CrossRefGoogle Scholar
  65. 65.
    Moll JR, Olive M, Vinson C (2000) Attractive interhelical electrostatic interactions in the proline- and acidic-rich region (PAR) leucine zipper subfamily preclude heterodimerization with other basic leucine zipper subfamilies. J Biol Chem 275(44):34826–34832CrossRefGoogle Scholar
  66. 66.
    Sharma G, Mavroidis C, Rege K, Yarmush ML, Budil D (2009) Computational studies of a protein-based nanoactuator for nanogripping applications. Int J Robot Res 28(4):421–435CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  • Gaurav Sharma
    • 1
  • Atul Dubey
    • 2
  • Constantinos Mavroidis
    • 3
  1. 1.Battelle Memorial InstituteColumbusUSA
  2. 2.Department of Chemical and Biochemical EngineeringRutgers UniversityPiscatawayUSA
  3. 3.Department of Mechanical and Industrial EngineeringNortheastern UniversityBostonUSA

Personalised recommendations