Biopolym. Cell. 2007; 23(1):35-44.
Molecular Biophysics
The binding of actinocin derivative with DNA fragments (Monte Carlo simulation)
1Shestopalova A. V.
  1. A. Usikov Institute of Radio Physics and Electronics, NAS of Ukraine
    12, Proskura Str., Kharkov, Ukraine, 61085

Abstract

The computer simulations of the interaction of DNA fragments and actinocin derivative (ActII) with ligand-target ratio 1:1 and 2:1 were carried out by a Monte Carlo method taking into account water environment. Low-energy molecular structures corresponding to the most probable models of two types of complexes – binding of ActII in minor groove and intercalation of ActII into GC-site with different complex stehiometry were obtained. The energetic and structural parameters of the complex formation were calculated. The stability of investigated complexes was conditioned by Van der Waals and electrostatic interactions as well as by the interaction with a solvent. The water molecules contribute to the stabilization of complexes due to the formation of water bridges between donor-acceptor groups of DNA fragments and ligands. Possible sizes of ActII binding sites in the minor groove were determined. They equaled 3-4 b.p. per the ligand molecule. The sizes of binding sites of intercalating ActII molecules into GC-site are obviously bigger than 4 b.p. per the ligand molecule. The results obtained are in agreement with the experimental data.
Keywords: DNA fragments, actinocin derivative, complexation, Monte Carlo method, size of binding site, hydration, molecular interaction

References

[1] Kruglova EB. Comparison of the effects of active cationic dye binding to DNA in the visible and UV regions. Vest Kharkiv Univer, N 525, Biofiz vestn. 2001, iss1 (8):27-33.
[2] Kruglova EB, Bolbukh TV, Gladkovskaya NA, Bliznyuk YuN. The binding of actinocin antibiotics to polyphosphate matrix. Biopolym Cell. 2005; 21(4):358-64.
[3] Fox KR, Webster R, Phelps RJ, Fokt I, Priebe W. Sequence selective binding of bis-daunorubicin WP631 to DNA. Eur J Biochem. 2004;271(17):3556-66.
[4] Chaires JB. Drug--DNA interactions. Curr Opin Struct Biol. 1998;8(3):314-20.
[5] Kruglova EB, Maleev VYa, Glibin EN, Veselkov AN. Physical mechanisms of interaction actinocin derivatives with DNA. 6. Spectrophotometric study of DNA complexes with derivatives actinocin with different length of methylene chains. Vest Kharkiv Univer N 560, Biofiz vestn. 2002. iss 1 (10):20-29.
[6] Maleev VYa, Semenov MA, Kruglova EB. A spectroscopic and calorimetric study of DNA complexation with a new series of actinocin derivatives (ActII-ActV). Anti-cancer drug design: biological and biophysical aspects of synthetic phenoxazone derivatives. Eds A. N. Veselkov, D. D. Davis. Sevastopol: SEVNTU press, 2002: 47-125.
[7] Kruglova EB, Gladkovskaia NA, Maleev VIa. [The use of the spectrophotometric analysis for the calculation of the thermodynamic parameters in actinocin derivative-DNA systems]. Biofizika. 2005;50(2):253-64.
[8] Maleev V, Semenov M, Kruglova E, Bolbukh T, Gasan A, Bereznyak E, et al. Spectroscopic and calorimetric study of DNA interaction with a new series of actinocin derivatives. J Mol Struct. 2003;645(2-3):145–58.
[9] Anishchenko DB, Bereznyak EG, Shestopalova AV, Maleev VYa. The study of molecular mechanisms of interaction of caffeine and actinocin derivatives with DNA molecular dynamics method. II. The role of various factors in the formation of the DNA-ligand complex. Vest Kharkiv Univer N 593, Biofiz vestn. 2003; Iss. 1 (12):13-9.
[10] Miroshnychenko KV, Shestopalova AV. Flexible docking of DNA fragments and actinocin derivatives. Molecular Simulation. 2005;31(8):567–74.
[11] Danilov VI, Zheltovsky NV, Slyusarchuk ON, Poltev VI, Alderfer JL. The study of the stability of Watson-Crick nucleic acid base pairs in water and dimethyl sulfoxide: computer simulation by the Monte Carlo method. J Biomol Struct Dyn. 1997;15(1):69-80.
[12] Alderfer JL, Danilov VI, Poltev VI, Slyusarchuk ON. A study of the hydration of deoxydinucleoside monophosphates containing thymine, uracil and its 5-halogen derivatives: Monte Carlo simulation. J Biomol Struct Dyn. 1999;16(5):1107-17.
[13] Metropolis N, Rosenbluth AW, Rosenbluth MN, Teller AH, Teller E. Equation of State Calculations by Fast Computing Machines. J Chem Phys. 1953;21(6):1087-92.
[14] Poltev VI, Malenkov GG, Gonzalez EJ, Teplukhin AV, Rein R, Shibata M, Miller JH. Modeling DNA hydration: comparison of calculated and experimental hydration properties of nuclic acid bases. J Biomol Struct Dyn. 1996;13(4):717-26.
[15] Teplukhin AV, Malenkov GG, Poltev VI. Monte Carlo simulation of DNA fragment hydration in the presence of alkaline cations using novel atom-atom potential functions. J Biomol Struct Dyn. 1998;16(2):289-300.
[16] Abraham F.F. Monte Carlo simulation of physical clusters of water molecules. J Chem Phys. 1974; 61(3):1221-5.
[17] Zhurkin VB, Poltev VI, Florent'ev VL. [Atom--atomic potential functions for conformational calculations of nucleic acids]. Mol Biol (Mosk). 1980;14(5):1116-30.
[18] Schmidt MW, Baldridge KS, Baatz JA, Elbert ST, Gordon MS, Jensen JH, Koseki S, Matsunaga N, Nguyen KA, Su A, Windus TL, Dupuis M, Montgomery JA. General atomic and molecular electronic structure system (CAMESS) J Comput Chem, 199;3 (14):1347-63.
[19] Subramanian PS, Beveridge DL. A theoretical study of the aqueous hydration of canonical B d(CGCGAATTCGCG): Monte Carlo simulation and comparison with crystallographic ordered water sites. J Biomol Struct Dyn. 1989;6(6):1093-122.
[20] Kopka ML, Goodsell DS, Baikalov I, Grzeskowiak K, Cascio D, Dickerson RE. Crystal structure of a covalent DNA-drug adduct: anthramycin bound to C-C-A-A-C-G-T-T-G-G and a molecular explanation of specificity. Biochemistry. 1994;33(46):13593-610.
[21] Saminadin P, Dautant A, Mondon M, Langlois D'estaintot B, Courseille C, Pr?cigoux G. Release of the cyano moiety in the crystal structure of N-cyanomethyl-N-(2-methoxyethyl)-daunomycin complexed with d(CGATCG). Eur J Biochem. 2000;267(2):457-64.
[22] Rohs R, Bloch I, Sklenar H, Shakked Z. Molecular flexibility in ab initio drug docking to DNA: binding-site and binding-mode transitions in all-atom Monte Carlo simulations. Nucleic Acids Res. 2005;33(22):7048-57.