Ligand-induced DNA conformational changes in proflavine minor groove-bound complexes studied by molecular dynamics simulation
Abstract
Background: Minor groove binding is a rate-limiting step in proflavine-DNA intercalation reaction. This step is believed also to be responsible for the sequence-dependent kinetics of proflavine binding to DNA. At the same time, most studies are focused on the final stage of the reaction – the intercalation complex, and there is a lack of data concerning the structure and stability of proflavine-DNA minor groove-bound complexes.
Objectives: The objective of this study was to investigate the stability of proflavine minor groove-bound complexes with DNA oligonucleotides of different sequence by molecular dynamics simulation and to analyze the DNA conformational changes caused by the proflavine binding.
Materials and methods: The molecular dynamics simulations of proflavine minor groove-bound complexes with poly(dA)·poly(dT) and poly(dCG)·poly(dCG) oligonucleotides of 30 bp length were done in program package AMBER12 with explicit water (SPC/E) and ions (NaCl 0.15 M) using force fields FF14SB for DNA and GAFF for ligand. The starting configurations of complexes were obtained by docking method in AutoDock 3.05. After multi-stage equilibration protocol, each system was simulated at T=300 K and p=1 bar for a 50 ns production phase. Then trajectories were post-processed in AMBERTools17 and VMD-1.9.3 packages.
Results: Our simulations confirm that proflavine-DNA minor groove-bound complexes are stable in the 50 ns time range but there are some structural rearrangements in them with respect to the initial structures. The narrowing of the DNA minor groove is observed in the proflavine binding site. In proflavine-poly(dCG)·poly(dCG) complex it is more pronounced and is accompanied by the BI/BII transitions in DNA and the reorientation of ligand. In proflavine-poly(dA)·poly(dT) complex the specific intermolecular hydrogen bonds are formed, which are optimized by the changes in opening and propeller twisting of involved AT-base pairs. Complexes are stabilized by the van der Waals and hydrophobic interactions, which are more favorable in the proflavine-poly(dA)·poly(dT) complex.
Conclusions: Our results show that the binding of proflavine to a minor groove of DNA induces the conformational changes in the DNA that are important for the resulting complex stability.
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References
Ferguson, L. R., & Denny, W. A. (1991). The genetic toxicology of acridines. Mutation Research, 258(2), 123-160. doi:10.1016/0165-1110(91)90006-H
Peacocke, A. R., & Skerrett, J. N. H. (1956). The interaction of aminoacridines with nucleic acids. Transactions of the Faraday Society, 52, 261-279. doi:10.1039/TF9565200261
Lerman, L. S. (1961). Structural considerations in the interaction of DNA and acridines. Journal of Molecular Biology, 3(1), 18-30. doi:10.1016/S0022-2836(61)80004-1
Luzzati, V., Masson, F., &Lerman, L. S. (1961). Interaction of DNA and proflavine: a small-angle X-ray scattering study. Journal of Molecular Biology, 3(5), 634-639. doi:10.1016/S0022-2836(61)80026-0
Lerman, L. S. (1963). The structure of the DNA-acridine complex. Biochemistry, 49(1), 94-102. doi:10.1073/pnas.49.1.94
Neville, D. M. Jr., & Davies, D. R. (1966). The interaction of acridine dyes with DNA: an X-ray diffraction and optical investigation. Journal of Molecular Biology, 17(1), 57-74. doi:10.1016/S0022-2836(66)80094-3
Neidle, S., Achari, A., Taylor, G. L., Berman, H. M., Carrell, H. L., Glusker, J. P., & Stallings, W. C. (1977). Structure of a dinucleoside phosphate-drug complex as model for nucleic acid-drug interaction. Nature, 269, 304-307. doi:10.1038/269304a0
Berman, H. M., Stallings, W., Carrell, H. L., Glusker, J. P., Neidle, S., Taylor, G., &Achari, A. (1979). Molecular and crystal structure of an intercalation complex: proflavine-cytidylyl-(3',5')-guanosine. Biopolymers, 18(10), 2405-2429. doi:10.1002/bip.1979.360181004
Shieh, H.-S., Berman, H. M., Dabrow, M., &Neidle, S. (1980). The structure of drug-deoxydinucleoside phosphate complex: generalized conformational behavior of intercalation complexes with RNA and DNA fragments. Nucleic Acids Research, 8(1), 85-97. doi:10.1093/nar/8.1.85
Maehigashi, T., Persil, O., Hud, N. V., & Williams, L.D. (2010). Crystal structure of proflavine in complex with DNA hexamer duplex. Protein Data Bank. Retrieved from: https://www.rcsb.org/structure/3FT6
Li, H. J., & Crothers, D. M. (1969). Relaxation studies of the proflavine-DNA complex: the kinetics of an intercalation reaction. Journal of Molecular Biology, 39(3), 461-477. doi:10.1016/0022-2836(69)90138-7
Ramstein, J., Dourlent, M., &Leng, M. (1972). Interaction between proflavine and deoxyribonucleic acid influence of DNA base composition. Biochemical and Biophysical Research Communications, 47(4), 874-882. doi:10.1016/0006-291X(72)90574-8
Ramstein, J., Ehrenberg, M., &Rigler, R. (1980). Fluorescence relaxation of proflavin-deoxyribonucleic acid interaction. Kinetic properties of a base-specific reaction. Biochemistry, 19(17), 3938-3948. doi:10.1021/bi00558a008
Marcandalli, B., Winzek, C., &Holzwarth, J. F. (1984). A laser temperature jump investigation of the interaction between proflavine and calf-thymus deoxyribonucleic acid at low and high ionic strength avoiding electric field effects. Berichte der Bunsengesellschaft fur PhysikalischeChemie, 88(4), 368-374. doi:10.1002/bbpc.19840880411
Marcandalli, B., Stange, G., &Holzwarth, J. F. (1988). Kinetics of the interaction of acridine dyes with nucleic acids. An iodine-laser temperature-jump investigation. Journal of the Chemical Society, Faraday Transactions 1, 84(8), 2807-2819. doi:10.1039/F19888402807
Alden, C. J., & Arnott, S. (1975). Visualization of planar drug intercalations in B-DNA. Nucleic Acids Research, 2(10), 1701-1717. doi:10.1093/nar/2.10.1701
Alden, C. J., & Arnott, S. (1977). Stereochemical model for proflavine intercalation in A-DNA. Nucleic Acids Research, 4(11), 3855-3861. doi:10.1093/nar/4.11.3855
Neidle, S., Pearl, L. H., Herzyk, P., & Berman, H. M. (1988). A molecular model for proflavine-DNA intercalation. Nucleic Acids Research, 16(18), 8999-9016. doi:10.1093/nar/16.18.8999
Herzyk, P., Neidle, S., &Goodfellow, J. M. (1992). Conformation and dynamics of drug-DNA intercalation. Journal of Biomolecular Structure and Dynamics, 10(1), 97-139. doi:10.1080/07391102.1992.10508633
Ruiz, R., Garcia, B., Ruisi, G., Silvestri, A., & Barone, G. (2009). Computational study of the interaction of proflavine with d(ATATATATAT)2 and d(GCGCGCGCGC)2. Journal of Molecular Structure:THEOCHEM, 915(1-3), 86-92. doi:10.1016/j.theochem.2009.08.022
Yoshida, N., Kiyota, Y., & Hirata, F. (2011). The electronic-structure theory of a large-molecular system in solution: application to the intercalation of proflavine with solvated DNA. Journal of Molecular Liquids, 159(1), 83-92. doi:10.1016/j.molliq.2010.04.019
Pack, G. R., Hashimoto, G. M., & Loew, G. H. (1981). Quantum chemical calculations on the two-step mechanism of proflavin binding to DNA. Annals of the New York Academy of Sciences, 367, 240-249. doi:10.1111/j.1749-6632.1981.tb50571.x
Islam, S. A., &Neidle, S. (1984). Nucleic acid binding drugs. X. A theoretical study of proflavine intercalation into RNA and DNA fragments: comparison with crystallographic results. Acta Crystallographica Section B, 40(4), 424-429. doi:10.1107/S010876818400241X
Sasikala, W. D., & Mukherjee, A. (2012). Molecular mechanism of direct proflavine-DNA intercalation: evidence for drug-induced minimum base-stacking penalty pathway. The Journal of Physical Chemistry B, 116(40), 12208-12212. doi:10.1021/jp307911r
Sasikala, W. D., & Mukherjee, A. (2013). Intercalation and de-intercalation pathway of proflavine through the minor and major grooves of DNA: roles of water and entropy. Physical Chemistry Chemical Physics, 15(17), 6446-6455. doi:10.1039/C3CP50501D
Sasikala, W. D., & Mukherjee, A. (2016). Structure and dynamics of proflavine association around DNA. Physical Chemistry Chemical Physics, 18(15), 10383-10391. doi:10.1039/C5CP07789C
Miroshnychenko, K. V., &Shestopalova, A. V. (2013, July). The study of different binding modes of proflavine with DNA and RNA sequences by molecular docking method: evidence for a proflavine as a minor groove binder. Paper presented at the 5th International Symposium “Methods and Applications of Computational Chemistry”, Kharkiv, Ukraine. Retrieved from: http://macc.org.ua/MACC-5/MACC5colored.pdf
Case, D. A., Cerutti, D. S., Cheatham, T. E. III, Darden, T. A., Duke, R. E., Giese, T. J., … Kollman P. A. (2017). AMBERTools17 [Computer software]. Retrieved from http://ambermd.org
Lu, X.-J., & Olson, W. K. (2008). 3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures. Nature Protocols, 3(7), 1213-1227. doi:10.1038/nprot.2008.104
Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., … Pople, J. A. (2004). Gaussian 03 (Revision E.01) [Computer software]. Gaussian, Inc., Wallingford CT.
Dupradeau, F.-Y., Pigache, A., Zaffran, T., Savineau, C., Lelong, R., Grivel, N., ... Cieplak P. (2010). The R.E.D. tools: advances in RESP and ESP charge derivation and force field library building. Physical Chemistry Chemical Physics, 12(28), 7821-7839. doi:10.1039/c0cp00111b
Morris, G. M., Goodsell, D. S., Halliday, R. S., Huey, R., Hart, W. E., Belew, R. K., & Olson, A. J. (1998). Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. Journal of Computational Chemistry, 19(14), 1639-1662.
doi:10.1002/(SICI)1096-987X(19981115)19:14%3C1639::AID-JCC10%3E3.0.CO;2-B
Berman, H. M., Olson, W. K., Beveridge D. L., Westbrook, J., Gelbin, A., Demeny, T., … Schneider, B. (1992). The nucleic acid database.A comprehensive relational database of three-dimensional structures of nucleic acids. Biophysical journal, 63(3), 751-759. doi:10.1016/S0006-3495(92)81649-1
Case, D. A., Darden, T. A., Cheatham, T. E. III, Simmerling, C. L., Wang, J., Duke, R. E., ... Kollman P. A. (2012). AMBER 12[Computer software]. Retrieved from http://ambermd.org
Maier, J. A., Martinez, C., Kasavajhala, K., Wickstrom, L., Hauser, K. E., & Simmerling, C. (2015). FF14SB: improving the accuracy of protein side chain and backbone parameters from FF99SB. Journal of Chemical Theory and Computation, 11(8), 3696-3713. doi:10.1021/acs.jctc.5b00255
Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A., & Case, D. A. (2004). Development and testing of a general AMBER force field. Journal of Computational Chemistry, 25(9), 1157-1174. doi:10.1002/jcc.20035
Berendsen, H. J. C., Grigera, J. R., &Straatsma, T. P. (1987). The missing term in effective pair potentials. The Journal of Physical Chemistry, 91(24), 6269-6271. doi:10.1021/j100308a038
Joung, I. S., & Cheatham, T. E. III (2009). Molecular dynamics simulations of the dynamic and energetic properties of alkali and halide ions using water-model-specific ion parameters. The Journal of Physical Chemistry B, 113(40), 13279-13290. doi:10.1021/jp902584c
Darden, T., York, D., & Pedersen, L. (1993). Particle mesh Ewald: an N•log(N) method for Ewald sums in large systems. The Journal of Chemical Physics, 98(12), 10089-10092. doi:10.1063/1.464397
Ryckaert, J.-P., Ciccotti, G., & Berendsen, H. J. C. (1977). Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. Journal of Computational Physics, 23(3), 327-341. doi:10.1016/0021-9991(77)90098-5
Berendsen, H. J. C., Postma, J. P. M., van Gunsteren, W. F., DiNola, A., &Haak, J. R. (1984). Molecular dynamics with coupling to an external bath. The Journal of Chemical Physics, 81(8), 3684-3690. doi:10.1063/1.448118
Roe, D. R., & Cheatham, T. E. III (2013). PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. Journal of Chemical Theory and Computation, 9(7), 3084-3095. doi:10.1021/ct400341p
Humphrey, W., Dalke, A., &Schulten, K. (1996). VMD-visual molecular dynamics. Journal of Molecular Graphics, 14(1), 33-38. doi:10.1016/0263-7855(96)00018-5
Miller, B. R. III, McGee, T. D. Jr., Swails, J. M., Homeyer, N., Gohlke, H., &Roitberg, A. E. (2012). MMPBSA.py: an efficient program for end-state free energy calculations. Journal of Chemical Theory and Computation, 8(9), 3314-3321. doi:10.1021/ct300418h
Tan, C., Tan, Y.-H., & Luo, R. (2007). Implicit nonpolar solvent models. The Journal of Physical Chemistry B, 111(42), 12263-12274. doi:10.1021/jp073399n
McQuarrie, D. A. (1976). Statistical Mechanics. New York: Harper & Row.
Rueda, M., Cubero, E., Laughton, C. A., & Orozco, M. (2004). Exploring the counterion atmosphere around DNA: what can be learned from molecular dynamics simulations? Biophysical Journal, 87(2), 800-811. doi:10.1529/biophysj.104.040451
Mocci, F., &Laaksonen, A. (2012). Insight into nucleic acid counterion interactions from inside molecular dynamics simulations is “worth its salt”. Soft Matter, 8(36), 9268-9284. doi:10.1039/C2SM25690H
Zgarbova, M., Otyepka, M., Sponer, J., Lankas, F., &Jurecka, P. (2014). Base pair fraying in molecular dynamics simulations of DNA and RNA. Journal of Chemical Theory and Computation, 10(8), 3177-3189. doi:10.1021/ct500120v
Fratini, A. V., Kopka, M. L., Drew, H. R., & Dickerson, R. E. (1982). Reversible bending and helix geometry in a B-DNA dodecamer: CGCGAATTBrCGCG. Journal of Biological Chemistry, 257(24), 14686-14707. Retrieved from: http://www.jbc.org/cgi/pmidlookup?view=long&pmid=7174662
Djuranovic, D., & Hartmann, B. (2003). Conformational characteristics and correlations in crystal structures of nucleic acid oligonucleotides: evidence for sub-states. Journal of Biomolecular Structure and Dynamics, 20(6), 771-788. doi:10.1080/07391102.2003.10506894
Wecker, K., Bonnet, M. C., Meurs, E. F., &Delepierre, M. (2002). The role of the phosphorus BI-BII transition in protein-DNA recognition: the NF-κB complex. Nucleic Acids Research, 30(20), 4452-4459. doi:10.1093/nar/gkf559
Djuranovic, D., Oguey, C., & Hartmann, B. (2004). The role of DNA structure and dynamics in the recognition of bovine papillomavirus E2 protein target sequences. Journal of Molecular Biology, 339(4), 785-796. doi:10.1016/j.jmb.2004.03.078
Robertson, J. C., & Cheatham, T. E. III (2015). DNA backbone BI/BII distribution and dynamics in E2 protein-bound environment determined by molecular dynamics simulations. The Journal of Physical Chemistry B, 119(44), 14111-14119. doi:10.1021/acs.jpcb.5b08486
Madhumalar, A., & Bansal, M. (2005). Sequence preference for BI/BII conformations in DNA: MD and crystal structure data analysis. Journal of Biomolecular Structure and Dynamics, 23(1), 13-27. doi:10.1080/07391102.2005.10507043
Heddi, B., Foloppe, N., Bouchemal, N., Hantz, E., & Hartmann, B. (2006). Quantification of DNA BI/BII backbone states in solution. Implications for DNA overall structure and recognition. Journal of the American Chemical Society, 128(28), 9170-9177. doi:10.1021/ja061686j
Ramakers, L. A. I., Hithell, G., May, J. J., Greetham, G. M., Donaldson, P. M., Towrie, M., ... Hunt, N. T. (2017). 2D-IR spectroscopy shows that optimized DNA minor groove binding of Hoechst33258 follows an induced fit model. The Journal of Physical Chemistry B, 121(6), 1295-1303. doi:10.1021/acs.jpcb.7b00345
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