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.
Key words
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Aksimentiev A (2010) Deciphering ionic current signatures of DNA transport through a nanopore. Nanoscale 2:468–483
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
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
Freddolino P, Harrison C, Liu Y, Schulten K (2010) Challenges in protein-folding simulations. Nat Phys 6:751–758
Frenkel D, Smit B (2002) Understanding molecular simulation from algorithms to applications. Academic, California
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
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
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
Beglov D, Roux B (1994) Finite representation of an infinite bulk system: Solvent boundary potential for computer simulations. J Chem Phys 100:9050–9063
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
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
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
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
Andersen H (1983) Rattle: A “velocity” version of the Shake algorithm for Molecular Dynamics calculations. J Comput Chem 52: 24–34
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
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
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
Xu D, Phillips JC, Schulten K (1996) Protein response to external electric fields: Relaxation, hysteresis, and echo. J Phys Chem 100: 12108–12121
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
Cruz-Chu ER, Aksimentiev A, Schulten K (2006) Water-silica force field for simulating nanodevices. J Phys Chem B 110: 21497–21508
Li J, Stein D, McMullan C, Branton D, Aziz MJ, Golovchenko JA (2001) Ion-beam sculpting at nanometre length scales. Nature 412: 166–169
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
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
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
Fologea D, Uplinger J, Thomas B, McNabb DS, Li J (2005) Slowing DNA translocation in a solid-state nanopore. Nano Lett 5: 1734–1737
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
Soni GV, Meller A (2007) Progress toward ultrafast DNA sequencing using solid-state nanopores. Clin Chem 53:1996–2001
Aksimentiev A, Brunner R, Cruz-Chu ER, Comer J, Schulten K (2009) Modeling transport through synthetic nanopores. IEEE Nanotechnol Mag 3:20–28
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
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
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
Kubo R, Toda M, Hashitsume N (1991) Statistical physics II: nonequilibrium statistical mechanics. Springer, New York
Koopman E, Lowe C (2006) Advantages of a Lowe-Andersen thermostat in molecular dynamics simulations. J Chem Phys 124:204103
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
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
Martinetz T, Schulten K (1994) Topology representing networks. Neural Netw 7:507–522
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
Coury L (1999) Conductance measurements part 1: theory. Curr Sep 18:91–96
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
Feig M, Pettitt BM (1998) Structural equilibrium of DNA represented with different force fields. Biophys J 75:134–149
van Dijk M, Bonvin AMJJ (2009) 3D-DART: a DNA structure modelling server. Nucleic Acids Res 37:W235–W239
Lavery R, Moakher M, Maddocks JH, Petkeviciute D, Zakrzewska K (2009) Conformational analysis of nucleic acids revisited: Curves+. Nucleic Acids Res 37: 5917–5929
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
Luan B, Aksimentiev A (2008) DNA attraction in monovalent and divalent electrolytes. J Am Chem Soc 130:15754–15755
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
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
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
Roux B (1996) Valence selectivity of the gramicidin channel: a molecular dynamics free energy perturbation study. Biophys J 71:3177–3185
Martyna GJ, Tobias DJ, Klein ML (1994) Constant pressure molecular dynamics algorithms. J Chem Phys 101:4177–4189
Feller S, MacKerell A Jr (2000) An improved empirical potential energy function for molecular simulations of phospholipids. J Phys Chem B 104:7510–7515
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
Humphrey W, Dalke A, Schulten K (1996) VMD—visual molecular dynamics. J Mol Graph 14:33–38
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
Faller M, Niederweis M, Schultz G (2004) The structure of a mycobacterial outer membrane channel. Science 303:1189–1192
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
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
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights 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