Skip to main content
SpringerLink
Log in

Optimization of the Molecular Dynamics Method for Simulations of DNA and Ion Transport Through Biological Nanopores

  • Protocol
  • First Online:
Nanopore-Based Technology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 870))

Abstract

Molecular dynamics (MD) simulations have become a standard method for the rational design and interpretation of experimental studies of DNA translocation through nanopores. The MD method, however, offers a multitude of algorithms, parameters, and other protocol choices that can affect the accuracy of the resulting data as well as computational efficiency. In this chapter, we examine the most popular choices offered by the MD method, seeking an optimal set of parameters that enable the most computationally efficient and accurate simulations of DNA and ion transport through biological nanopores. In particular, we examine the influence of short-range cutoff, integration timestep and force field parameters on the temperature and concentration dependence of bulk ion conductivity, ion pairing, ion solvation energy, DNA structure, DNA–ion interactions, and the ionic current through a nanopore.

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 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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. Aksimentiev A (2010) Deciphering ionic current signatures of DNA transport through a nanopore. Nanoscale 2:468–483

    Article  CAS  Google Scholar 

  2. MacKerell AD Jr, Bashford D, Bellott M, Dunbrack RL Jr, Evanseck J, Field MJ et al (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem B 102:3586–3616

    Article  CAS  Google Scholar 

  3. Cornell WD, Cieplak P, Bayly CI, Gould IR, Merz KM Jr, Ferguson DM et al (1995) A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J Am Chem Soc 117:5179–5197

    Article  CAS  Google Scholar 

  4. Freddolino P, Harrison C, Liu Y, Schulten K (2010) Challenges in protein-folding simulations. Nat Phys 6:751–758

    Article  CAS  Google Scholar 

  5. Frenkel D, Smit B (2002) Understanding molecular simulation from algorithms to applications. Academic, California

    Google Scholar 

  6. Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E et al (2005) Scalable molecular dynamics with NAMD. J Comput Chem 26:1781–1802

    Article  CAS  Google Scholar 

  7. Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79:926–935

    Article  CAS  Google Scholar 

  8. Miyamoto S, Kollman PA (1992) SETTLE: an analytical version of the SHAKE and RATTLE algorithm for rigid water molecules. J Comput Chem 13:952–962

    Article  CAS  Google Scholar 

  9. Beglov D, Roux B (1994) Finite representation of an infinite bulk system: Solvent boundary potential for computer simulations. J Chem Phys 100:9050–9063

    Article  CAS  Google Scholar 

  10. Joung IS, Cheatham TE III (2008) Determination of alkali and halide monovalent ion parameters for use in explicitly solvated biomolecular simulations. J Phys Chem B 112: 9020–9041

    Article  CAS  Google Scholar 

  11. MacKerell A Jr, Banavali N (2000) All-atom empirical force field for nucleic acids: II. application to molecular dynamics simulations of dna and rna in solution. J Comput Chem 21: 105–120

    Article  CAS  Google Scholar 

  12. Perez A, Marchan I, Svozil D, Sponer J, Cheatham TE, Laughton CA et al (2007) Refinement of the AMBER force field for nucleic acids: Improving the description of α/γ conformers. Biophys J 92:3817–3829

    Article  CAS  Google Scholar 

  13. MacKerrel AD, Feig M, Brooks CL III (2004) Extending the treatment of backbone energetics in protein force fields: limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations. J Comput Chem 25: 1400–1415

    Article  Google Scholar 

  14. Andersen H (1983) Rattle: A “velocity” version of the Shake algorithm for Molecular Dynamics calculations. J Comput Chem 52: 24–34

    CAS  Google Scholar 

  15. Benz R, Castro-Román F, Tobias D, White S (2005) Experimental validation of molecular dynamics simulations of lipid bilayers: a new approach. Biophys J 88: 805–817

    Article  CAS  Google Scholar 

  16. Sonne J, Jensen M, Hansen F, Hemmingsen L, Peters G (2007) Reparameterization of all-atom dipalmitoylphosphatidylcholine lipid parameters enables simulation of fluid bilayers at zero tension. Biophys J 92:4157–4167

    Article  CAS  Google Scholar 

  17. Klauda J, Venable R, Freites J, O’Connor J, Tobias D, Mondragon-Ramirez C et al (2010) Update of the charmm all-atom additive force field for lipids: validation on six lipid types. J Phys Chem B 114:7830–7843

    Article  CAS  Google Scholar 

  18. Xu D, Phillips JC, Schulten K (1996) Protein response to external electric fields: Relaxation, hysteresis, and echo. J Phys Chem 100: 12108–12121

    Article  CAS  Google Scholar 

  19. Heng JB, Aksimentiev A, Ho C, Marks P, Grinkova YV, Sligar S et al (2006) The electromechanics of DNA in a synthetic nanopore. Biophys J 90:1098–1106

    Article  CAS  Google Scholar 

  20. Cruz-Chu ER, Aksimentiev A, Schulten K (2006) Water-silica force field for simulating nanodevices. J Phys Chem B 110: 21497–21508

    Article  CAS  Google Scholar 

  21. Li J, Stein D, McMullan C, Branton D, Aziz MJ, Golovchenko JA (2001) Ion-beam sculpting at nanometre length scales. Nature 412: 166–169

    Article  CAS  Google Scholar 

  22. Li J, Gershow M, Stein D, Brandin E, Golovchenko JA (2003) DNA molecules and configurations in a solid-state nanopore microscope. Nat Mater 2:611–615

    Article  CAS  Google Scholar 

  23. Chang H, Kosari F, Andreadakis G, Alam MA, Vasmatzis G, Bashir R (2004) DNA-mediated fluctuations in ionic current through silicon oxide nanopore channels. Nano Lett 4: 1551–1556

    Article  CAS  Google Scholar 

  24. Heng JB, Ho C, Kim T, Timp R, Aksimentiev A, Grinkova YV et al (2004) Sizing DNA using a nanometer-diameter pore. Biophys J 87: 2905–2911

    Article  CAS  Google Scholar 

  25. Fologea D, Uplinger J, Thomas B, McNabb DS, Li J (2005) Slowing DNA translocation in a solid-state nanopore. Nano Lett 5: 1734–1737

    Article  CAS  Google Scholar 

  26. Storm AJ, Chen JH, Zandbergen HW, Dekker C (2005) Translocation of double-strand DNA through a silicon oxide nanopore. Phys Rev E Stat Nonlin Soft Matter Phys 71: 051903–051913

    Article  CAS  Google Scholar 

  27. Soni GV, Meller A (2007) Progress toward ultrafast DNA sequencing using solid-state nanopores. Clin Chem 53:1996–2001

    Article  CAS  Google Scholar 

  28. Aksimentiev A, Brunner R, Cruz-Chu ER, Comer J, Schulten K (2009) Modeling transport through synthetic nanopores. IEEE Nanotechnol Mag 3:20–28

    Article  Google Scholar 

  29. Darden T, York D, Pedersen L (1993) Particle mesh Ewald. An N·log(N) method for Ewald sums in large systems. J Chem Phys 98:10089–10092

    Article  CAS  Google Scholar 

  30. Batcho PF, Case DA, Schlick T (2001) Optimized particle-mesh Ewald/multiple-time step integration for molecular dynamics simulations. J Chem Phys 115:4003–4018

    Article  CAS  Google Scholar 

  31. Skeel RD, Hardy DJ, Phillips JC (2006) Correcting mesh-based force calculations to conserve both energy and momentum in molecular dynamics simulations. J Comput Phys 225:1–5

    Article  Google Scholar 

  32. Kubo R, Toda M, Hashitsume N (1991) Statistical physics II: nonequilibrium statistical mechanics. Springer, New York

    Google Scholar 

  33. Koopman E, Lowe C (2006) Advantages of a Lowe-Andersen thermostat in molecular dynamics simulations. J Chem Phys 124:204103

    Article  CAS  Google Scholar 

  34. Aksimentiev A, Schulten K (2005) Imaging alpha-hemolysin with molecular dynamics: Ionic conductance, osmotic permeability and the electrostatic potential map. Biophys J 88: 3745–3761

    Article  CAS  Google Scholar 

  35. Schmid R, Miah AM, Sapunov VN (2000) A new table of the thermodynamic quantities of ionic hydration: values and some applications (enthalpy–entropy compensation and born radii). Phys Chem Chem Phys 2:97–102

    Article  CAS  Google Scholar 

  36. Martinetz T, Schulten K (1994) Topology representing networks. Neural Netw 7:507–522

    Article  Google Scholar 

  37. Bhattacharya S, Muzard J, Payet L, Bockelman U, Aksimentiev A, Viasnoff V (2011) Rectification of the current in alpha-hemolysin pore depends on the cation type: the alkali series probed by MD simulations and experiments. J Phys Chem C Nanomater Interfaces 115:4255–4264

    Article  CAS  Google Scholar 

  38. Coury L (1999) Conductance measurements part 1: theory. Curr Sep 18:91–96

    CAS  Google Scholar 

  39. Pezeshki S, Chimerel C, Bessonov AN, Winterhalter M, Kleinekathofer U (2009) Understanding ion conductance on a molecular level: An all-atom modeling of the bacterial porin OmpF. Biophys J 97:1898–1906

    Article  CAS  Google Scholar 

  40. Feig M, Pettitt BM (1998) Structural equilibrium of DNA represented with different force fields. Biophys J 75:134–149

    Article  CAS  Google Scholar 

  41. van Dijk M, Bonvin AMJJ (2009) 3D-DART: a DNA structure modelling server. Nucleic Acids Res 37:W235–W239

    Article  Google Scholar 

  42. Lavery R, Moakher M, Maddocks JH, Petkeviciute D, Zakrzewska K (2009) Confor­mational analysis of nucleic acids revisited: Curves+. Nucleic Acids Res 37: 5917–5929

    Article  CAS  Google Scholar 

  43. Luan B, Aksimentiev A (2008) Electro-osmotic screening of the DNA charge in a nanopore. Phys Rev E Stat Nonlin Soft Matter Phys 78:021912

    Article  Google Scholar 

  44. Luan B, Aksimentiev A (2008) DNA attraction in monovalent and divalent electrolytes. J Am Chem Soc 130:15754–15755

    Article  CAS  Google Scholar 

  45. Maffeo C, Schöpflin R, Brutzer H, Stehr R, Aksimentiev A, Wedemann G et al (2010) DNA–DNA interactions in tight supercoils are described by a small effective charge density. Phys Rev Lett 105:158101

    Article  Google Scholar 

  46. Zhao Q, Comer J, Dimitrov V, Aksimentiev A, Timp G (2008) Stretching and unzipping nucleic acid hairpins using a synthetic nanopore. Nucleic Acids Res 36:1532–1541

    Article  CAS  Google Scholar 

  47. Comer J, Dimitrov V, Zhao Q, Timp G, Aksimentiev A (2009) Microscopic mechanics of hairpin DNA translocation through synthetic nanopores. Biophys J 96: 593–608

    Article  CAS  Google Scholar 

  48. Roux B (1996) Valence selectivity of the gramicidin channel: a molecular dynamics free energy perturbation study. Biophys J 71:3177–3185

    Article  CAS  Google Scholar 

  49. Martyna GJ, Tobias DJ, Klein ML (1994) Constant pressure molecular dynamics algorithms. J Chem Phys 101:4177–4189

    Article  CAS  Google Scholar 

  50. Feller S, MacKerell A Jr (2000) An improved empirical potential energy function for molecular simulations of phospholipids. J Phys Chem B 104:7510–7515

    Article  CAS  Google Scholar 

  51. Brünger AT (1992) X-PLOR, Version 3.1: a system for x-ray crystallography and NMR. The Howard Hughes Medical Institute and Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT

    Google Scholar 

  52. Humphrey W, Dalke A, Schulten K (1996) VMD—visual molecular dynamics. J Mol Graph 14:33–38

    Article  CAS  Google Scholar 

  53. Mathé J, Aksimentiev A, Nelson DR, Schulten K, Meller A (2005) Orientation discrimination of single stranded DNA inside the α-hemolysin membrane channel. Proc Natl Acad Sci USA 102:12377–12382

    Article  Google Scholar 

  54. Faller M, Niederweis M, Schultz G (2004) The structure of a mycobacterial outer membrane channel. Science 303:1189–1192

    Article  CAS  Google Scholar 

  55. Derrington I, Butler T, Collins M, Manrao E, Pavlenok M, Niederweis M et al (2010) Nanopore DNA sequencing with MspA. Proc Natl Acad Sci USA 107:16060

    Article  CAS  Google Scholar 

  56. Yoo J., Aksimentiev A. (2012) Improved parameterization of Li+, Na+, K+, and Mg2+ ions for all-atom molecular dynamics simulations of nucleic acid systems. Journal of Physical Chemistry Letters, 3:45–50

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL, USA

    David B. Wells, Swati Bhattacharya, Rogan Carr, Christopher Maffeo, Anthony Ho & Jeffrey Comer

  2. Department of Physics and Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, USA

    Aleksei Aksimentiev

Authors
  1. David B. Wells
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Swati Bhattacharya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rogan Carr
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christopher Maffeo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anthony Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jeffrey Comer
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aleksei Aksimentiev
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aleksei Aksimentiev .

Editor information

Editors and Affiliations

  1. , Department of Physics, Clarkson University, Clarkson Ave. 8, Potsdam, 13699, New York, USA

    Maria E. Gracheva

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Wells, D.B. et al. (2012). Optimization of the Molecular Dynamics Method for Simulations of DNA and Ion Transport Through Biological Nanopores. In: Gracheva, M. (eds) Nanopore-Based Technology. Methods in Molecular Biology, vol 870. Humana Press. https://doi.org/10.1007/978-1-61779-773-6_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-773-6_10

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-772-9

  • Online ISBN: 978-1-61779-773-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation