Advertisement

Future Prospects

  • Norma M. AllewellEmail author
  • Igor A. Kaltashov
  • Linda O. Narhi
  • Ivan Rayment
Chapter
Part of the Biophysics for the Life Sciences book series (BIOPHYS, volume 6)

Abstract

This chapter illustrates the dynamic, evolving nature of molecular biophysics by providing perspectives on future prospects in three major areas: X-ray and neutron scattering, mass spectrometry, and therapeutic drug development. In all three areas, major advances in the biological sciences, development of powerful new experimental and computational tools, and urgent real-world challenges are driving rapid progress. These developments have enabled and encouraged biophysicists to focus increasingly on studying systems of various sizes and the interactions between their components, rather than simply on their isolated constituents. As the examples demonstrate, these interactions are often transient, and may occur in massive macromolecular complexes, between macromolecules, or between macromolecules and ligands. A diverse set of emerging and advancing technologies are likely to spur future developments. These include advances in methods that enable individual molecules to be studied at atomic resolution; high throughput methods, increasing automation, development of massive databases that allow comparison and analysis of data of many types gathered worldwide; and increasingly powerful computational methods that enable ever larger systems to be modeled at high resolution. Finally, the emerging field of synthetic biology will create exciting opportunities to create, explore, and manipulate the biophysics of novel systems.

Keywords

Advances in computation Database development High throughput automation Macromolecular interactions Mass spectrometry Membrane proteins Single molecule methods Structural biology Therapeutic drug development X-ray and neutron scattering 

References

  1. 1.
    Bilokapic S, Schwartz TU (2012) 3D ultrastructure of the nuclear pore complex. Curr Opin Cell Biol 24:86–91PubMedCrossRefGoogle Scholar
  2. 2.
    Corbett KD, Harrison SC (2012) Molecular architecture of the yeast monopolin complex. Cell Rep 1:583–589PubMedCrossRefGoogle Scholar
  3. 3.
    Boutet S, Lomb L, Williams GJ, Barends TR, Aquila A, Doak RB, Weierstall U, DePonte DP, Steinbrener J, Shoeman RL, Messerschmidt M, Barty A, White TA, Kassemeyer S, Kirian RA, Seibert MM, Montanez PA, Kenney C, Herbst R, Hart P, Pines J, Haller G, Gruner SM, Philipp HT, Tate MW, Hromalik M, Koerner LJ, van Bakel N, Morse J, Ghonsalves W, Arnlund D, Bogan MJ, Caleman C, Fromme R, Hampton CY, Hunter MS, Johansson LC, Katona G, Kupitz C, Liang M, Martin AV, Nass K, Redecke L, Stellato F, Timneanu N, Wang D, Zatsepin NA, Schafer D, Defever J, Neutze R, Fromme P, Spence JC, Chapman HN, Schlichting I (2012) High-resolution protein structure determination by serial femtosecond crystallography. Science 337:362–364PubMedCrossRefGoogle Scholar
  4. 4.
    Petoukhov MV, Svergun DI (2013) Applications of small-angle X-ray scattering to biomacromolecular solutions. Int J Biochem Cell Biol 45(2):429–437PubMedCrossRefGoogle Scholar
  5. 5.
    Annesley TM (2003) Ion suppression in mass spectrometry. Clin Chem 49:1041–1044PubMedCrossRefGoogle Scholar
  6. 6.
    Lengqvist J, Svensson R, Evergren E, Morgenstern R, Griffiths WJ (2004) Observation of an intact non-covalent homotrimer of detergent-solubilised rat microsomal glutathione transferase 1 by electrospray mass spectrometry. J Biol Chem 279(14):13311–13316, M310958200PubMedCrossRefGoogle Scholar
  7. 7.
    Barrera NP, Di Bartolo N, Booth PJ, Robinson CV (2008) Micelles protect membrane complexes from solution to vacuum. Science 321:243–246PubMedCrossRefGoogle Scholar
  8. 8.
    Pan Y, Stocks BB, Brown L, Konermann L (2009) Structural characterization of an integral membrane protein in its natural lipid environment by oxidative methionine labeling and mass spectrometry. Anal Chem 81:28–35PubMedCrossRefGoogle Scholar
  9. 9.
    Wen JZ, Zhang H, Gross ML, Blankenship RE (2009) Membrane orientation of the FMO antenna protein from Chlorobaculum tepidum as determined by mass spectrometry-based footprinting. Proc Natl Acad Sci U S A 106:6134–6139PubMedCrossRefGoogle Scholar
  10. 10.
    Sobott F, McCammon MG, Hernandez H, Robinson CV (2005) The flight of macromolecular complexes in a mass spectrometer. Philos Trans A Math Phys Eng Sci 363:379–389, discussion 389–391PubMedCrossRefGoogle Scholar
  11. 11.
    Heck AJR (2008) Native mass spectrometry: a bridge between interactomics and structural biology. Nat Methods 5:927–933PubMedCrossRefGoogle Scholar
  12. 12.
    Abzalimov RR, Kaltashov IA (2010) Electrospray ionization mass spectrometry of highly heterogeneous protein systems: protein ion charge state assignment via incomplete charge reduction. Anal Chem 82:7523–7526PubMedCrossRefGoogle Scholar
  13. 13.
    Bohrer BC, Mererbloom SI, Koeniger SL, Hilderbrand AE, Clemmer DE (2008) Biomolecule analysis by ion mobility spectrometry. Annu Rev Anal Chem 1:293–327CrossRefGoogle Scholar
  14. 14.
    Damen C, Chen W, Chakraborty A, van Oosterhout M, Mazzeo J, Gebler J, Schellens J, Rosing H, Beijnen J (2009) Electrospray ionization quadrupole ion-mobility time-of-flight mass spectrometry as a tool to distinguish the lot-to-lot heterogeneity in N-glycosylation profile of the therapeutic monoclonal antibody trastuzumab. J Am Soc Mass Spectrom 20:2021–2033PubMedCrossRefGoogle Scholar
  15. 15.
    Bagal D, Zhang H, Schnier PD (2008) Gas-phase proton-transfer chemistry coupled with TOF mass spectrometry and ion mobility-MS for the facile analysis of poly(ethylene glycols) and PEGylated polypeptide conjugates. Anal Chem 80:2408–2418PubMedCrossRefGoogle Scholar
  16. 16.
    Collins MO, Choudhary JS (2008) Mapping multiprotein complexes by affinity purification and mass spectrometry. Curr Opin Biotechnol 19:324–330PubMedCrossRefGoogle Scholar
  17. 17.
    Monti M, Cozzolino M, Cozzolino F, Vitiello G, Tedesco R, Flagiello A, Pucci P (2009) Puzzle of protein complexes in vivo: a present and future challenge for functional proteomics. Expert Rev Proteomics 6:159–169PubMedCrossRefGoogle Scholar
  18. 18.
    Terentiev AA, Moldogazieva NT, Shaitan KV (2009) Dynamic proteomics in modeling of the living cell. Protein–protein interactions. Biochemistry (Mosc) 74:1586–1607CrossRefGoogle Scholar
  19. 19.
    Malik R, Dulla K, Nigg EA, Korner R (2010) From proteome lists to biological impact-tools and strategies for the analysis of large MS data sets. Proteomics 10:1270–1283PubMedCrossRefGoogle Scholar
  20. 20.
    Zhou M, Robinson CV (2010) When proteomics meets structural biology. Trends Biochem Sci 35:522–529PubMedCrossRefGoogle Scholar
  21. 21.
    Gavin AC, Maeda K, Kuhner S (2011) Recent advances in charting protein–protein interaction: mass spectrometry-based approaches. Curr Opin Biotechnol 22:42–49PubMedCrossRefGoogle Scholar
  22. 22.
    Sardiu ME, Washburn MP (2011) Building protein–protein interaction networks with proteomics and informatics tools. J Biol Chem 286:23645–23651PubMedCrossRefGoogle Scholar
  23. 23.
    Sinz A (2010) Investigation of protein–protein interactions in living cells by chemical crosslinking and mass spectrometry. Anal Bioanal Chem 397:3433–3440PubMedCrossRefGoogle Scholar
  24. 24.
    Zhu Y, Guo TN, Park JE, Li X, Meng W, Datta A, Bern M, Lim SK, Sze SK (2009) Elucidating in vivo structural dynamics in integral membrane protein by hydroxyl radical footprinting. Mol Cell Proteomics 8:1999–2010PubMedCrossRefGoogle Scholar
  25. 25.
    Xie J, Schultz PG (2006) A chemical toolkit for proteins—an expanded genetic code. Nat Rev Mol Cell Biol 7:775–782PubMedCrossRefGoogle Scholar
  26. 26.
    Narhi L (2012) In: Narhi L (ed) (2013) Biophysical characterization during protein therapeutic development. SpringerGoogle Scholar
  27. 27.
    Mahler H-C, Friess W, Grauschopf U, Kiese S (2009) Protein aggregation: pathways, induction factors and analysis. J Pharm Sci 98:2909–2934PubMedCrossRefGoogle Scholar
  28. 28.
    Chen S, Lau H, Brodsky Y, Kleemann GR, Latypov RF (2010) The use of native cation-exchange chromatography to study aggregation and phase separation of monoclonal antibodies. Protein Sci 19:1191–1204PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Norma M. Allewell
    • 1
    Email author
  • Igor A. Kaltashov
    • 2
  • Linda O. Narhi
    • 3
  • Ivan Rayment
    • 4
  1. 1.Department of Cell Biology and Molecular GeneticsUniversity of MarylandCollege ParkUSA
  2. 2.Department of ChemistryUniversity of Massachusetts-AmherstAmherstUSA
  3. 3.Research and Development, Amgen, Inc.Thousand OaksUSA
  4. 4.Department of BiochemistryUniversity of Wisconsin-MadisonMadisonUSA

Personalised recommendations