Positively and Negatively Hydrated Counterions in Molecular Dynamics Simulations of DNA Double Helix


  • S. Perepelytsya Bogolyubov Institute for Theoretical Physics of the Nat. Acad. of Sci. of Ukraine




DNA, counterion, hydration, residence time, molecular dynamics


The DNA double helix is a polyanionic macromolecule that is neutralized in water solutions by metal ions (counterions). The property of counterions to stabilize the water network (positive hydration) or to make it friable (negative hydration) is important in terms of the physical mechanisms of stabilization of the DNA double helix. In the present research, the effects of positive hydration of Na+ counterions and negative hydration of K+ and Cs+ counterions incorporated into the hydration shell of the DNA double helix have been studied using molecular dynamics simulations. The results have shown that the dynamics of the hydration shell of counterions depends on the region of the double helix: minor groove, major groove, and outside the macromolecule. The longest average residence time has been observed for water molecules contacting with the counterions localized in the minor groove of the double helix (about 50 ps for Na+ and lower than 10 ps for K+ and Cs+). The estimated potentials of the mean force for the hydration shells of counterions show that the water molecules are constrained too strongly, and the effect of negative hydration for K+ and Cs+ counterions has not been observed in the simulations. The analysis has shown that the effects of counterion hydration can be described more accurately with water models having lower dipole moments.


W. Saenger. Principles of Nucleic Acid Structure (Springer, 1984) [ISBN: 978-0471524175]. https://doi.org/10.1007/978-1-4612-5190-3

J.D. Watson, F.H.C. Crick. A structure of deoxyribose nucleic acid. Nature 171, 737 (1953). https://doi.org/10.1038/171737a0

R.E. Franklin, R.G. Gosling. Molecular configuration in sodium thymonucleate. Nature 171, 740 (1953). https://doi.org/10.1038/171740a0

M.H.F. Wilkins, A.R. Stokes, H.R. Wilson. Molecular structure of deoxypentose nucleic acid. Nature 171, 738 (1953). https://doi.org/10.1038/171738a0

Yu.P. Blagoy, V.L. Galkin, G.O. Gladchenko et al. The Complexes of Nucleic Acids with Metal Cations in Solutions (Naukova Dumka, 1991) (in Russian) [ISBN: 5-12-002499-0].

A.V. Sivolob. Physics of DNA (Kyiv University, 2011) (in Ukrainian) [ISBN: 978-966-439-468-3].

A. Vologodskii, Biophysics of DNA (Cambridge Univ. Press, 2015) [ISBN: 9781139542371]. https://doi.org/10.1017/CBO9781139542371

V.Ya. Maleev, M.A. Semenov, M.A. Gassan, V.I. Kashpur. Physical properties of the DNA-water system. Biofizika 38, 768 (1993) (in Russian).

H.R. Drew, R.M. Wing, T. Takano, C. Broka, S. Takana, K. Itakura, R.E. Dickerson. Structure of a B-DNA dodecamer: Conformation and dynamics. Proc. Natl. Acad. Sci. USA 78, 2179 (1981). https://doi.org/10.1073/pnas.78.4.2179

V. Tereshko, G. Minasov, M. Egli. A "hydrat-ion" spine in a B-DNA minor groove J. Am. Chem. Soc. 121, 3590 (1999). https://doi.org/10.1021/ja984346+

F. Mocci, A. Laaksonen. Insights into nucleic acid counterion interactions from inside molecular dynamics simulation is "worth its salt". Soft Matter 8, 9268 (2012). https://doi.org/10.1039/c2sm25690h

D. Laage,T. Elsaesser, J.T. Hynes. Water dynamics in the hydration shells of biomolecules. Chem. Rev. 117, 10694 (2017). https://doi.org/10.1021/acs.chemrev.6b00765

E. Dubou'e-Dijon, A.C. Fogarty, J.T. Hynes, D. Laage. Dynamical disorder in the DNA hydration shell. J. Am. Chem. Soc. 138, 7610 (2016). https://doi.org/10.1021/jacs.6b02715

N.A. Ismailov. Electro Chemistry of Solutions (Chemistry, 1976) (in Russian).

P.R. Smirnov, V.N. Trostin. Structures of the nearest surroundings of the K+, Rb+, and Cs+ ions in aqueous solutions of their salts. Russian J. of General Chemistry 77 (12), 2101 (2007). https://doi.org/10.1134/S1070363207120043

I.R. Yukhnovskii, M.F. Golovko. Statistical Theory of Classical Equilibrium Systems (Naukova Dumka, 1980) (in Russian).

G.S. Manning. The molecular theory of polyelectrolyte solutions with applications to the electrostatic properties of polynucleotides. Quarterly Reviews of Biophysics 11, 179 (1978). https://doi.org/10.1017/S0033583500002031

M.D. Frank-Kamenetskii, V.V. Anshelevich, A.V. Lukashin. Polyelectrolyte model of DNA. Soviet Physics Uspekhi 30, 317 (1987). https://doi.org/10.1070/PU1987v030n04ABEH002833

R. Das, T.T. Mills, L.W. Kwok, G.S. Maskel, I.S. Millett, S. Doniach, K.D. Finkelstein, D. Herschlag, L. Pollack. Counterion distribution around DNA probed by solution X-ray scattering. Phys. Rev. Lett. 90, 188103 (2003). https://doi.org/10.1103/PhysRevLett.90.188103

K. Andersen, R. Das, H.Y. Park, H. Smith, L.W. Kwok, J.S. Lamb, E.J. Kirkland, D. Herschlag, K.D. Finkelstein, L. Pollack. Spatial distribution of competing ions around DNA in solution. Phys. Rev. Lett. 93, 248103 (2004). https://doi.org/10.1103/PhysRevLett.93.248103

K. Andresen, X. Qiu, S.A. Pabit, J.S. Lamb, H.Y. Park, L.W. Kwok, L. Pollack. Mono- and trivalent ions around DNA: A small-angle scattering study of competition and interactions. Biophys. J. 95, 287 (2008). https://doi.org/10.1529/biophysj.107.123174

X. Qiu, K. Andresen, J.S. Lamb, L.W. Kwok, L. Pollack. Abrupt transition from a free, repulsive to a condensed, attractive DNA phase, induced by multivalent polyamine cations. Phys. Rev. Lett. 101, 228101 (2008). https://doi.org/10.1103/PhysRevLett.101.228101

S.M. Perepelytsya, S.N. Volkov. Ion mode in the DNA low-frequency vibration spectra. Ukr. J. Phys. 49, 1074 (2004).

S.M. Perepelytsya, S.N. Volkov. Counterion vibrations in the DNA low-frequency spectra. Eur. Phys. J. E 24, 261 (2007). https://doi.org/10.1140/epje/i2007-10236-x

L.A. Bulavin, S.N. Volkov, S.Yu. Kutovy, S.M. Perepelytsya. Observation of the DNA ion-phosphate vibrations. Rep. Nat. Acad. Sci. of Ukraine No. 11, 69 (2007).

S.M. Perepelytsya, S.N. Volkov. Intensities of DNA ion-phosphate modes in the low-frequency Raman spectra. Eur. Phys. J. E 31, 201 (2010). https://doi.org/10.1140/epje/i2010-10566-6

S.M. Perepelytsya, S.N. Volkov. Conformational vibrations of ionic lattice in DNA: Manifestation in the low-frequency Raman spectra. J. Mol. Liq. 5, 1182 (2011).

S.M. Perepelytsya, S.N. Volkov. Vibrations of ordered counterions around left-and right-handed DNA double helixes. J. Phys.: Conf. Ser. 438, 012013 (2013). https://doi.org/10.1088/1742-6596/438/1/012013

S.M. Perepelytsya, G.M. Glibitskiy, S.N. Volkov. Texture formation in DNA films with alkali metal chlorides. Biopolymers 99, 508 (2013). https://doi.org/10.1002/bip.22209

O.O. Liubysh, O.M. Alekseev, S.Yu. Tkachov, S.M. Perepelytsya. Effect of ionic ordering in conductivity experiments of DNA aqueous solutions. Ukr. J. Phys. 59, 2071 (2014). https://doi.org/10.15407/ujpe59.05.0479

F. Mocci, G. Saba. Molecular dynamics simulations of A. T-rich oligomers: sequence-specific binding of Na+ in the minor groove of B-DNA. Biopolymers 68, 471 (2003). https://doi.org/10.1002/bip.10334

R. Lavery, J.H. Maddocks, M. Pasi, K. Zakrzewska. Analyzing ion distribution around DNA. Nucleic Acids Res. 42, 8138 (2014). https://doi.org/10.1093/nar/gku504

M. Pasi, J.H. Maddocks, R. Lavery. Analyzing ion distributions around DNA: sequence-dependence of potassium ion distributions from microsecond molecular dynamics. Nucleic Acids Res. 43, 2412 (2015). https://doi.org/10.1093/nar/gkv080

O.O. Liubysh, A.V. Vlasiuk, S.M. Perepelytsya. Structuring of counterions around DNA double helix: a molecular dynamics study. Ukr. J. Phys. 49, 1074 (2015).

A. Atzori, S. Liggi, A. Laaksonen, M. Porcu, A.P. Lyubartsev, G. Saba, F. Mocci. Base sequence specificity of counterion binding to DNA: what can MD simulations tell us? Canadian J. of Chemistry 94 (12), 1181 (2016). https://doi.org/10.1139/cjc-2016-0296

S. Perepelytsya. Hydration of counterions interacting with DNA double helix: a molecular dynamics study. J. Mol. Mod. 24, 171 (2018). https://doi.org/10.1007/s00894-018-3704-x

S. Perepelytsya, J. Uliˇcn'y, A. Laaksonen, F. Mocci. Pattern preferences of DNA nucleotide motifs by polyamines putrescine2+, spermidine3+ and spermine4+. Nucleic Acids Res. 47, 6084 (2019). https://doi.org/10.1093/nar/gkz434

J.C. Phillips, R. Braun,W.Wang, J. Gumbart, E. Tajkhorshid, E. Villa, C. Chipot, R.D. Skeel, L. Kale, K. Schulten. Scalable molecular dynamics with NAMD J. Comp. Chem. 26, 1781 (2005). https://doi.org/10.1002/jcc.20289

N. Foloppe, A.D. MacKerell, jr. All-atom empirical force field for nucleic acids: I. Parameter optimization based on small molecule and condensed phase macromolecular target data. J. Comp. Chem. 21, 86 (2000). https://doi.org/10.1002/(SICI)1096-987X(20000130)21:2<86::AID-JCC2>3.0.CO;2-G

A.D. MacKerell, jr., N. Banavali. All-atom empirical force field for nucleic acids: II. Application to molecular dynamics simulations of DNA and RNA in solution. J. Comp. Chem. 21, 105 (2000). https://doi.org/10.1002/(SICI)1096-987X(20000130)21:2<105::AID-JCC3>3.0.CO;2-P

J.P. Ryckaert, G. Ciccotti, H.J.C. Berendsen. Numerical integration of the Cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. J. Comp. Chem. 32, 327 (1977). https://doi.org/10.1016/0021-9991(77)90098-5

W.L. Jorgensen, J. Chandrasekhar, J.D. Madura, R.W. Impey, M.L. Klein. Comparison of simple potential functions for simulating liguids. J. Chem. Phys. 79, 926 (1983). https://doi.org/10.1063/1.445869

D. Beglov, B. Roux. Finite Representation of an infinite bulk system: solvent boundary potential for computer simulations. J. Chem. Phys. 100, 9050 (1994). https://doi.org/10.1063/1.466711

W. Humphrey, A. Dalke, K. Schulten. VMD - Visual Molecular Dynamics. J. Molec. Graphics 14.1, 33 (1996). https://doi.org/10.1016/0263-7855(96)00018-5

B.G. Levine, J.E. Stone, A. Kolhmeyer. Fast analysis of molecular dynamics trajectories with graphics processing units - radial distribution function hystogramming. J. Comp. Phys. 230, 3556 (2011). https://doi.org/10.1016/j.jcp.2011.01.048

M. Pekka, N. Lennart. Structure and dynamics of TIP3P, SPC, and SPC/E water models at 298 K. J. Phys. Chem. A 105, 9954 (2001). https://doi.org/10.1021/jp003020w

S. Koneshan, J.C. Rasaiah, R.M. Lynden-Bell, S.H. Lee. Solvent structure, dynamics, and ion mobility in aqueous solutions at 25 ∘C. J. Phys. Chem. B 102, 4193 (1998). https://doi.org/10.1021/jp980642x

L.D. Landau, E.M. Lifshitz. Mechanics (Butterworth-Heinemann, 2001).

V.N. Byakov, V.G. Petukhov, A.M. Sukhanovskaya, V.G. Firsov. Behavior of Solvation Shell Molecules in an Alternating Electric Field. Preprint ITEP-52 (ITEP, 1985) (in Russian).

C. Kittel. Introduction to Solid State Physics (Wiley, 1954) [ISBN: 978-0-471-41526-85]. https://doi.org/10.1063/1.3061720

A.V. Gubskaya, P.G. Kusalik. The total molecular dipole moment for liquid water. J. Chem. Phys. 117, 5290 (2002). https://doi.org/10.1063/1.1501122

J. Ramstein, R. Lavery. Energetic coupling between DNA bending and base pair opening. Proc. Natl. Acad. Sci. USA 85, 7231 (1988). https://doi.org/10.1073/pnas.85.19.7231

S.Y. Liem, P.L.A. Popelier, M. Leslie. Simulation of liquid water using a high-rank quantum topological electrostatic potential. International J. of Quantum Chem. 99, 685 (2004). https://doi.org/10.1002/qua.20025

P.G. Kusalik, I.M. Svishchev. The spatial structure in liquid water. Science 265, 1219 (1994). https://doi.org/10.1126/science.265.5176.1219

H.J.C. Berendsen, J.R. Grigera, T.P. Straatsma. The missing term in effective pair potentials. J. Phys. Chem. 91, 6269 (1987). https://doi.org/10.1021/j100308a038

M-L. Tan, J.T. Fischer, A. Chandra, B.R. Brooks, T. Ichiye. A temperature of maximum density in soft sticky dipole water. Chem. Phys. Lett. 376, 646 (2003). https://doi.org/10.1016/S0009-2614(03)01044-3

K. Kiyohara, K.E. Gubbins, A.Z. Panagiotopoulos. Phase coexistence properties of polarizable water models. Mol. Phys. 94, 803 (1998). https://doi.org/10.1080/00268979809482372




How to Cite

Perepelytsya, S. (2020). Positively and Negatively Hydrated Counterions in Molecular Dynamics Simulations of DNA Double Helix. Ukrainian Journal of Physics, 65(6), 510. https://doi.org/10.15407/ujpe65.6.510



Physics of liquids and liquid systems, biophysics and medical physics