Skip to main content
SpringerLink
Log in

Geometric Simulation of Flexible Motion in Proteins

  • Protocol
  • First Online:
Protein Dynamics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1084))

Abstract

This chapter describes the use of physically simplified analysis and simulation methods—pebble-game rigidity analysis, coarse-grained elastic network modeling, and template-based geometric simulation—to explore flexible motion in protein structures. Substantial amplitudes of flexible motion can be explored rapidly in an all-atom model, retaining realistic covalent bonding, steric exclusion, and a user-defined network of noncovalent polar and hydrophobic interactions, using desktop computing resources. Detailed instructions are given for simulations using FIRST/FRODA software installed on a UNIX/Linux workstation. Other implementations of similar methods exist, particularly NMSim and FRODAN, and are available online. Topics covered include rigidity analysis and constraints, geometric simulation of flexible motion, targeting between known structures, and exploration of motion along normal mode eigenvectors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Wells SA, Dove MT, Tucker MG, Trachenko K (2002) Real-space rigid-unit-mode analysis of dynamic disorder in quartz, cristobalite and amorphous silica. J Phys Condens Matter 14(18):4645–4657

    Article  CAS  Google Scholar 

  2. Sartbaeva A, Wells SA, Treacy MMJ, Thorpe MF (2006) The flexibility window in zeolites. Nat Mater 5(12):962–965

    Article  PubMed  CAS  Google Scholar 

  3. Wells SA, Sartbaeva A (2012) Template-based geometric simulation of flexible frameworks. Materials 5:415–431 (Special issue “Computer modelling of microporous materials”)

    Article  Google Scholar 

  4. Wells S, Menor S, Hespenheide B, Thorpe MF (2005) Constrained geometric simulation of diffusive motion in proteins. Phys Biol 2(4):S127–S136. doi:10.1088/1478-3975/2/4/S07

    Article  PubMed  CAS  Google Scholar 

  5. Jacobs DJ, Rader AJ, Kuhn LA, Thorpe MF (2001) Protein flexibility predictions using graph theory. Proteins 44(2):150–165

    Article  PubMed  CAS  Google Scholar 

  6. Jimenez-Roldan JE, Freedman RB, Romer RA, Wells SA (2012) Rapid simulation of protein motion: merging flexibility, rigidity and normal mode analyses. Phys Biol 9(1):016008. doi:10.1088/1478-3975/9/1/016008

    Article  PubMed  CAS  Google Scholar 

  7. Li H, Wells SA, Jimenez-Roldan JE, Romer RA, Zhao Y, Sadler PJ, O’Connor PB (2012) Protein flexibility is key to cisplatin crosslinking in calmodulin. Protein Sci 21(9):1269–1279. doi:10.1002/pro.2111

    Article  PubMed  CAS  Google Scholar 

  8. Burkoff NS, Varnai C, Wells SA, Wild DL (2012) Exploring the energy landscapes of protein folding simulations with Bayesian computation. Biophys J 102(3):446a

    Article  Google Scholar 

  9. Amin NT, Wallis AK, Wells SA, Rowe ML, Williamson RA, Howard MJ, Freedman RB (2012) High-resolution NMR studies of structure and dynamics of human ERp27 indicate extensive inter-domain flexibility. Biochem J 450:321. doi:10.1042/BJ20121635

    Article  Google Scholar 

  10. Farrell DW, Speranskiy K, Thorpe MF (2010) Generating stereochemically acceptable protein pathways. Proteins 78(14):2908–2921

    Article  PubMed  CAS  Google Scholar 

  11. Ahmed A, Rippmann F, Barnickel G, Gohlke H (2011) A normal mode-based geometric simulation approach for exploring biologically relevant conformational transitions in proteins. J Chem Inf Model 51(7):1604–1622. doi:10.1021/ci100461k

    Article  PubMed  CAS  Google Scholar 

  12. Kruger DM, Ahmed A, Gohlke H (2012) NMSim web server: integrated approach for normal mode-based geometric simulations of biologically relevant conformational transitions in proteins. Nucleic Acids Res 40(Web Server issue):W310–W316. doi:10.1093/nar/gks478

    Article  PubMed  Google Scholar 

  13. Schrodinger, LLC (2010) The PyMOL molecular graphics system, Version 1.3r1

    Google Scholar 

  14. Word JM, Lovell SC, Richardson JS, Richardson DC (1999) Asparagine and glutamine: using hydrogen atom contacts in the choice of side-chain amide orientation. J Mol Biol 285(4):1735–1747. doi:10.1006/jmbi.1998.2401

    Article  PubMed  CAS  Google Scholar 

  15. Suhre K, Sanejouand YH (2004) ElNemo: a normal mode web server for protein movement analysis and the generation of templates for molecular replacement. Nucleic Acids Res 32(Web Server issue):W610–W614. doi:10.1093/nar/gkh368

    Article  PubMed  CAS  Google Scholar 

  16. Rader AJ, Hespenheide BM, Kuhn LA, Thorpe MF (2002) Protein unfolding: rigidity lost. Proc Natl Acad Sci U S A 99(6):3540–3545. doi:10.1073/pnas.062492699

    Article  PubMed  CAS  Google Scholar 

  17. Cozzini P, Kellogg GE, Spyrakis F, Abraham DJ, Costantino G, Emerson A, Fanelli F, Gohlke H, Kuhn LA, Morris GM, Orozco M, Pertinhez TA, Rizzi M, Sotriffer CA (2008) Target flexibility: an emerging consideration in drug discovery and design. J Med Chem 51(20):6237–6255

    Article  PubMed  CAS  Google Scholar 

  18. Wells SA, Jimenez-Roldan JE, Roemer RA (2009) Comparative analysis of rigidity across protein families. Phys Biol 6(4):046005. doi:10.1088/1478-3975/6/4/046005

    Article  PubMed  CAS  Google Scholar 

  19. Heal JW, Jimenez-Roldan JE, Wells SA, Freedman RB, Romer RA (2012) Inhibition of HIV-1 protease: the rigidity perspective. Bioinformatics 28(3):350–357. doi:10.1093/bioinformatics/btr683

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physics, University of Bath, Bath, UK

    Stephen A. Wells

Authors
  1. Stephen A. Wells
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Bioinformatics and Genomic, University of North Carolina at Charlott, Charlotte, North Carolina, USA

    Dennis R. Livesay

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media,New York

About this protocol

Cite this protocol

Wells, S.A. (2014). Geometric Simulation of Flexible Motion in Proteins. In: Livesay, D. (eds) Protein Dynamics. Methods in Molecular Biology, vol 1084. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-658-0_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-658-0_10

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-657-3

  • Online ISBN: 978-1-62703-658-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation