AN OPTIMIZED PROTOCOL FOR IN VACUO MOLECULAR DYNAMICS SIMULATION AND TRAJECTORY ANALYSIS OF MODIFIED DNA DUPLEXES
Adamiak Ryszard W. *, Bielecki Łukasz
Institute of Bioorganic Chemistry, Polish Academy of Sciences,
61-704 Poznań, Noskowskiego 12/14
adamiakr@ibch.poznan.pl bielecki@ibch.poznan.pl
DOI: 10.12921/cmst.1996.02.01.07-16
OAI: oai:lib.psnc.pl:475
Abstract:
This paper presents an optimized protocol for in vacuo molecular dynamics studies of short DNA duplexes containing modified nucleosides. The example studied is an 11 base pair DNA duplex modified with l,N6-ethenodeoxyadenosine (dεA) located opposite deoxyguanosine. A complex molecular dynamics trajectory was subjected to statistical cluster analysis. Groups (clusters) of similar conformations, which can be statistically identified after energy minimization of the trajectory results, have been analyzed with particular regard to the estimation of intrinsic stability of the duplex (hydrogen bonding and base stacking). The modified residue was found to form two hydrogen bonds within the d ε A / d G base pair, which stabilize the duplex, thus allowing its conformation to remain close to regular B-DNA.
References:
[1] Saenger, W. “Principles of Nucleic Acids Structure”, Springer Verlag,
Heidelberg (1984)
[2] Singer, B., Antoccia, A., Basu, A. K., Dosanjh, M. K., Frankel-Conrat, H.,
Gallagher, P. E„ Kusmierek, J. T„ Qiu, Z. H. & Rydberg, B. (1992) Proc.Natl.
Acad. Sci. USA 89, 9386-9390
[3] Leonard, N. J., (1992) Chemtracts – Biochemistry & Mol. Biol. 3, 273-297
[4] de los Santos, C., Kouchakdjian, M„ Yarema, K., Basu, A., Essigman, J. &
Patel, D. J. (1991) Biochemistry 30, 1828-1835
[5] Leonard, G. A., McAuley-Hecht, K. E., Gibson, N. J., Brown, T., Watson, W.
P., & Hunter, W. N. (1994) Biochemistry IS, 4755-4761
[6] Zagórowska, I., Skalski, B., Bielecki, L., Popenda, M„ Biala, E., Paszyc, S.,
Verrall, R. & Adamiak, R. W., in preparation
[7] Kuliński, T. (1996) Computational Meth. Sci. Tech. 1,43-54
[8] van Gunsteren, W. F. & Berendsen, H. J. C. (1990) Angew. Chem. Int. Ed. Engl.
29, 992-1023
[9] Kumar, S„ Duan, Y„ Kollman, P. A. & Rosenberg, J. M. (1994) J. Biomol. Str.
Dyn. 12, 487-525
[10] Weiner, S. J., Kollman, P. A., Nguyen, D. T. & Case, D. A. (1986) J. Comp.
Chem. 7, 230-252
[11] Lavery, R. & Sklenar, H. (1988)./ Biomol. Str. Dvn. 6, 63-91
[12] Walkowiak, R. & Podlesny, A. (1995) Rocz. AR Pozn. CCLXXVIII. Algor.
Biometr. Stat. 17, 73-88
This paper presents an optimized protocol for in vacuo molecular dynamics studies of short DNA duplexes containing modified nucleosides. The example studied is an 11 base pair DNA duplex modified with l,N6-ethenodeoxyadenosine (dεA) located opposite deoxyguanosine. A complex molecular dynamics trajectory was subjected to statistical cluster analysis. Groups (clusters) of similar conformations, which can be statistically identified after energy minimization of the trajectory results, have been analyzed with particular regard to the estimation of intrinsic stability of the duplex (hydrogen bonding and base stacking). The modified residue was found to form two hydrogen bonds within the d ε A / d G base pair, which stabilize the duplex, thus allowing its conformation to remain close to regular B-DNA.
[1] Saenger, W. “Principles of Nucleic Acids Structure”, Springer Verlag,
Heidelberg (1984)
[2] Singer, B., Antoccia, A., Basu, A. K., Dosanjh, M. K., Frankel-Conrat, H.,
Gallagher, P. E„ Kusmierek, J. T„ Qiu, Z. H. & Rydberg, B. (1992) Proc.Natl.
Acad. Sci. USA 89, 9386-9390
[3] Leonard, N. J., (1992) Chemtracts – Biochemistry & Mol. Biol. 3, 273-297
[4] de los Santos, C., Kouchakdjian, M„ Yarema, K., Basu, A., Essigman, J. &
Patel, D. J. (1991) Biochemistry 30, 1828-1835
[5] Leonard, G. A., McAuley-Hecht, K. E., Gibson, N. J., Brown, T., Watson, W.
P., & Hunter, W. N. (1994) Biochemistry IS, 4755-4761
[6] Zagórowska, I., Skalski, B., Bielecki, L., Popenda, M„ Biala, E., Paszyc, S.,
Verrall, R. & Adamiak, R. W., in preparation
[7] Kuliński, T. (1996) Computational Meth. Sci. Tech. 1,43-54
[8] van Gunsteren, W. F. & Berendsen, H. J. C. (1990) Angew. Chem. Int. Ed. Engl.
29, 992-1023
[9] Kumar, S„ Duan, Y„ Kollman, P. A. & Rosenberg, J. M. (1994) J. Biomol. Str.
Dyn. 12, 487-525
[10] Weiner, S. J., Kollman, P. A., Nguyen, D. T. & Case, D. A. (1986) J. Comp.
Chem. 7, 230-252
[11] Lavery, R. & Sklenar, H. (1988)./ Biomol. Str. Dvn. 6, 63-91
[12] Walkowiak, R. & Podlesny, A. (1995) Rocz. AR Pozn. CCLXXVIII. Algor.
Biometr. Stat. 17, 73-88
