Abstract
The phenomenon of DNA hole transport (HT) has attracted of scientists for several decades, mainly due to its potential application in molecular electronics. As electron holes mostly localize on purine bases in DNA, the majority of scientific effort has been invested into chemically modifying the structures of adenine and guanine in order to increase their HT-mediating properties. In this work we examine an alternative, never yet explored, way of affecting the HT efficiency by forcing electron holes to localize on pyrimidine bases and move between them. Using an enhanced and revised version of our previously developed QM/MM model, we perform simulations of HT through polyadenine, polycytosine, polyguanine, and polythymine stacks according to a multistep hopping mechanism. From these simulations, kinetic parameters for HT are obtained. The results indicate a particularly high efficiency of cytosine→cytosine hopping, which is about ten times higher than the G → G hopping. We also discuss possible improvement of cytosine HT by modifying the oxidoreductive properties of complementary guanine residues.
Similar content being viewed by others
References
Ladik J (1959) Investigation of the electronic structure of desoxyribonucleic acid I. Approximate calculation of the π-electron overlap between adjacent nucleotide bases. Probable consequences. Acta Physiol Hung 11(3):239–258
Eley DD, Spivey DI (1962) Semiconductivity of organic substances. Part 9.—nucleic acid in the dry state. Trans Faraday Soc 58:411–415
Seidel CAM (1996) Nucleobase-specific quenching of fluorescent dyes. 1. Nucleobase one-electron redox potentials and their correlation with static and dynamic quenching efficiencies. J Phys Chem 100(13):5541–5553
Steenken S, Jovanovic SV (1997) How easily oxidizable is DNA? One-electron reduction potentials of adenosine and guanosine radicals in aqueous solution. J Am Chem Soc 119(3):617–618
Porath D, Bezryadin A, de Vries S, Dekker C (2000) Direct measurement of electrical transport through DNA molecules. Nature 403(6770):635–638
Wan C, Fiebig T, Schiemann O, Barton JK, Zewail AH (2000) Femtosecond direct observation of charge transfer between bases in DNA. Proc Natl Acad Sci 97(26):14052–14055
Meggers E, Michel-Beyerle ME, Giese B (1998) Sequence dependent long range hole transport in DNA. J Am Chem Soc 120(49):12950–12955
Kelley SO, Barton JK (1999) Electron transfer between bases in double helical DNA. Science 283(5400):375–381
Lewis FD, Liu X, Liu J, Miller SE, Hayes RT, Wasielewski MR (2000) Direct measurement of hole transport dynamics in DNA. Nature 406(6791):51–53
Núñez ME, Barton JK (2000) Probing DNA charge transport with metallointercalators. Curr Opin Chem Biol 4(2):199–296
De Pablo PJ, Moreno-Herrero F, Colchero J, Herrero JG, Baró AM, Ordejón P, Soler JM, Artacho E (2000) Absence of dc-conductivity in λ-DNA. Phys Rev Lett 85(23):4992–4995
Lewis JP, Cheatham TE, Starikov EB, Wang H, Sankey OF (2003) Dynamically amorphous character of electronic states in poly(dA)−poly(dT) DNA. J Phys Chem B 107(11):2581–2587
Steenken S, Telo JP, Novais HM, Candeias LP (1992) One-electron-reduction potentials of pyrimidine bases, nucleosides, and nucleotides in aqueous solution. Consequences for DNA redox chemistry. J Am Chem Soc 114(12):4701–4709
Oyler NA, Adamowicz L (1994) Theoretical ab initio calculations of the electron affinity of thymine. Chem Phys Lett 219(3–4):223–227
Smith DMA, Smets J, Adamowicz L (1999) Anions of the hydrogen-bonded uracil dimer. Ab initio theoretical study. J Phys Chem A 103(29):5784–5790
Yamagami R, Kobayashi K, Tagawa S (2009) Dynamics of the delocalized charges of a radical anion in a·T DNA duplexes. Chem Eur J 15(45):12201–12203
Genereux JC, Barton JK (2010) Mechanisms for DNA charge transport. Chem Rev 110(3):1642–1662
Venkatramani R, Keinan S, Balaeff A, Beratan DN (2011) Nucleic acid charge transfer: black, white and gray. Coord Chem Rev 255(7–8):635–648
Siriwong K, Voityuk AA (2012) Electron transfer in DNA. WIREs Comput Mol Sci 2(5):780–794
Kurnikov IV, Tong GSM, Madrid M, Beratan DN (2002) Hole size and energetics in double helical DNA: competition between quantum delocalization and solvation localization. J Phys Chem B 106(1):7–10
Voityuk AA (2005) Charge transfer in DNA: hole charge is confined to a single base pair due to solvation effects. J Chem Phys 122(20):204904
Burin AL, Uskov DB (2008) Strong localization of positive charge in DNA induced by its interaction with environment. J Chem Phys 129(2):025101
Priyadarshy S, Risser SM, Beratan DN (1996) DNA is not a molecular wire: protein-like electron-transfer predicted for an extended π-electron system. J Phys Chem 100(44):17678–17682
Lewis FD, Wu T, Zhang Y, Letsinger RL, Greenfield SR, Wasielewski MR (1997) Distance-dependent electron transfer in DNA hairpins. Science 277(5326):673–676
Jortner J, Bixon M, Langenbacher T, Michel-Beyerle ME (1998) Charge transfer and transport in DNA. Proc Natl Acad Sci USA 95(22):12759–12765
Delaney S, Barton JK (2003) Long-range DNA charge transport. J Org Chem 68(17):6475–6483
Takada T, Kawai K, Fujitsuka M, Majima T (2004) Direct observation of hole transfer through double-helical DNA over 100 Å. Proc Natl Acad Sci USA 101(39):14002–14006
Marcus RA (1956) On the theory of oxidation-reduction reactions involving electron transfer. I. J Chem Phys 24(5):966
Conron SM, Thazhathveetil AK, Wasielewski MR, Burin AL, Lewis FD (2010) Direct measurement of the dynamics of hole hopping in extended DNA G-tracts. An unbiased random walk. J Am Chem Soc 132(41):14388–14390
Bixon M, Giese B, Wessely S, Langenbacher T, Michel-Beyerle ME, Jortner J (1999) Long-range charge hopping in DNA. Proc Natl Acad Sci USA 96(21):11713–11716
Takada T, Kawai K, Cai X, Sugimoto A, Fujitsuka M, Majima T (2004) Charge separation in DNA via consecutive adenine hopping. J Am Chem Soc 126(4):1125–1129
Lin S-H, Fujitsuka M, Tetsuro M (2016) Excess-electron transfer in DNA by a fluctuation-assisted hopping mechanism. J Phys Chem B 120(4):660–666
Park MJ, Fujitsuka M, Kawai K, Majima T (2011) Direct measurement of the dynamics of excess electron transfer through consecutive thymine sequence in DNA. J Am Chem Soc 133(39):15320–15323
Henderson PT, Jones D, Hampikian G, Kan Y, Schuster GB (1999) Long-distance charge transport in duplex DNA: the phonon-assisted polaron-like hopping mechanism. Proc Natl Acad Sci USA 96(15):8353–8358
Murphy CJ, Arkin MR, Jenkins Y, Ghatlia ND, Bossmann SH, Turro NJ, Barton JK (1993) Long-range photoinduced electron transfer through a DNA helix. Science 262(5136):1025–1029
Kawai K, Hayashi M, Majima T (2012) HOMO energy gap dependence of hole-transfer kinetics in DNA. J Am Chem Soc 134(10):4806–4811
Giese B, Amaudrut J, Köhler AK, Spormann M, Wessely S (2001) Direct observation of hole transfer through DNA by hopping between adenine bases and by tunnelling. Nature 412(6844):318–320
Xiang L, Palma JL, Bruot C, Mujica V, Ratner MA, Tao N (2015) Intermediate tunnelling–hopping regime in DNA charge transport. Nat Chem 7(3):221–226
Okasada Y, Kawai K, Majima T (2013) Kinetics of charge transfer through DNA across guanine–cytosine repeats intervened by adenine–thymine base pair(s). Bull Chem Soc Jpn 86(1):25–30
Kawai K, Majima T (2013) Hole transfer kinetics of DNA. Acc Chem Res 46(11):2616–2625
Cooke MS, Evans MD, Dizdaroglu M, Lunec J (2003) Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J 17(10):1195–1214
Heller A (2000) On the hypothesis of cathodic protection of genes. Faraday Discuss 116:1–13
Merino EJ, Barton JK (2007) Oxidation by DNA charge transport damages conserved sequence block II, a regulatory element in mitochondrial DNA. Biochemistry 46(10):2805–2811
Rothemund PWK (2006) Folding DNA to create nanoscale shapes and patterns. Nature 440(7082):279–302
Okamoto A, Tanaka K, Saito I (2004) DNA logic gates. J Am Chem Soc 126(30):9458–9463
Nakatani K, Dohno C, Saito I (2000) Modulation of DNA-mediated hole-transport efficiency by changing superexchange electronic interaction. J Am Chem Soc 122(24):5893–5894
Saito I (2002) Design of intelligent nucleobases and DNA HOMO mapping. Nucleic Acids Res Suppl 2:5–6
Okamoto A, Tanaka K, Saito I (2003) Rational design of a DNA wire possessing an extremely high hole transport ability. J Am Chem Soc 125(17):5066–5071
Volobuyev M, Adamowicz L (2005) Computational model of hole transport in DNA. J Phys Chem B 109(2):1048–1054
Volobuyev M, Saint-Martin H, Adamowicz L (2007) A molecular dynamics calculations of hole transfer rates in DNA strands. J Phys Chem B 111(37):11083–11089
Pavanello M, Adamowicz L, Volobuyev M, Mennucci B (2010) Modeling hole transport in wet and dry DNA. J Phys Chem B 114(13):4416–4423
Smith DMA, Adamowicz L (2001) A dynamic model for electron transport in DNA. J Phys Chem B 105(38):9345–9354
Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery Jr JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian 09, revision a.02. Gaussian, Inc., Wallingford, CT
Abraham MJ, Murtola T, Schulz R, Páll S, Smith JC, Hess B, Lindahl E (2015) GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1–2:19–25
Duan Y, Wu C, Chowdhury S, Lee MC, Xiong G, Zhang W, Yang R, Cieplak P, Luo R, Lee T, Caldwell J, Wang J, Kollman P (2003) A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J Comput Chem 24(16):1999–2012
Bayly CI, Cieplak P, Cornell WD, Kollman PA (1993) A well-behaved electrostatic potential based method using charge restraints for determining atom-centered charges: the RESP model. J Phys Chem 97(40):10269–10280
Jorgensen WL, Chandrasekhar J, Madura JD (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79(2):926–935
Parsons J, Holmes JB, Rojas JM, Tsai J, Strauss CEM (2005) Practical conversion from torsion space to cartesian space for in silico protein synthesis. J Comput Chem 26(10):1063–1069
Mastryukov VS, Fan K, Boggs JE (1995) The effect of methylation on the structure of uracil. J Mol Struct 346:173–186
Eckart C (1935) Some studies concerning rotating axes and polyatomic molecules. Phys Rev 47(7):552–558
Thompson EJ, DePaul AJ, Patel SS, Sorin EJ (2010) Evaluating molecular mechanical potentials for helical peptides and proteins. PLoS ONE 5(4):e10056
Lavery R, Moakher M, Maddocks JH, Petkeviciute D, Zakrzewska K (2009) Conformational analysis of nucleic acids revisited: curves+. Nucleic Acids Res 37(17):5917–5929
Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF chimera - a visualization system for exploratory research and analysis. J Comput Chem 25(13):1605–1612
Giese B (2002) Long-distance electron transfer through DNA. Annu Rev Biochem 71:51–70
Wagenknecht H-A (2006) Electron transfer processes in DNA: mechanisms, biological relevance and applications in DNA analytics. Nat Prod Rep 23(6):973–1006
Slavícek P, Winter B, Faubel M, Bradforth SE, Jungwirth P (2009) Ionization energies of aqueous nucleic acids: photoelectron spectroscopy of pyrimidine nucleosides and ab initio calculations. J Am Chem Soc 131(18):6460–6467
Colsky J, Meiselas LE, Rosen SJ, Schulman I (1955) Response of patients with leukemia to 8-azaguanine. Blood. 10(5):482–492
Seela F, Jiang D, Xu K (2009) 8-Aza-2′-deoxyguanosine: base pairing, mismatch discrimination and nucleobase anion fluorescence sensing in single-stranded and duplex DNA. Org Biomol Chem 7(17):3463–3473
Acknowledgments
All calculations were performed using the computational resources provided by the University of Arizona and by the Interdisciplinary Centre for Mathematical and Computational Modelling at the University of Warsaw (as part of G18-6 grant), for which we are grateful.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Online Resource 1
(PDF 211 kb)
Rights and permissions
About this article
Cite this article
Woźniak, A.P., Leś, A. & Adamowicz, L. Theoretical modeling of DNA electron hole transport through polypyrimidine sequences: a QM/MM study. J Mol Model 25, 97 (2019). https://doi.org/10.1007/s00894-019-3976-9
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00894-019-3976-9