title: Dynamic conformational states of DNA containing T.T or BrdU.T mispaired bases: wobble H-bond pairing versus cross-strand inter-atomic contacts.
abstract: The dynamic structure of 11-mer DNA duplexes of different sequences with or without homopyrimidine (T.T, or BrdU.T) mismatches was studied by molecular dynamics (MD) simulations on a time scale from 200 ps to 1 ns. The conformational analysis suggests that in mismatched duplexes the formation of classical T.T wobble H-bonding pairing is nearest-neighbor sequence-dependent and, in most cases, three-centered H-bonds and numerous alternative close cross-strand interatomic contacts exist. Thus, in duplex W1, where the central triplet is 5'd(CTA).d(TTG), two wobble conformations W upward arrow (alphabeta) and W downward arrow (betaalpha) are formed and exchange rapidly at 300 K. In contrast, when the central triplet is 5'd(TTT).d(ATA) (W2 duplex) wobble conformations are rarely observed at 300 K, and the T.T mispair most often adopts a "twisted" conformation with one largely persistent normal H-bond, plus a stable cross-strand contact involving a T flanking base. However, at elevated temperature (400 K) the same W2 duplex shows frequent exchange between the two classical wobble conformations (alphabeta<-->betaalpha), as is in the case when the central triplet is 5'd(TBrdUT).d(ATA) (W3 duplex at 300 K). It is suggested that in the W2 sequence, restrictions due to thymine-methyl/pi interactions prevent the formation of wobble pairing and thermal activation energy, and/or the chemical replacement of T by BrdU are required in order for the T(BrdU).T mismatch to adopt and exchange between wobble conformations. The specific short and/or long-lived (double/triple) cross-strand dynamic interactions in W1, W2 and W3 duplexes are throughout characterized. These frequent atomic encounters exemplify possible inter-strand charge transfer pathways in the studied DNA molecules.
authors.affiliation: Department of Nuclear Medicine and Radiobiology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, QC, J1H 5N4, Canada. Tsvetan.Gantchev@USherbrooke.ca
authors.forename: Tsvetan G
authors.initials: TG
authors.lastname: Gantchev
authors.forename: Sylvain
authors.initials: S
authors.lastname: Cecchini
authors.forename: Darel J
authors.initials: DJ
authors.lastname: Hunting
mesh_terms: D001482:Base Composition; D004247:DNA / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009690:Nucleic Acid Conformation
chemical_list: D004247:DNA
references.citation: J Mol Biol. 1995 Feb 10;246(1):209-26
references.pmid: 7853398
references.citation: Science. 1987 Oct 23;238(4826):498-504
references.pmid: 3310237
references.citation: Biochemistry. 1999 Mar 23;38(12):3468-77
references.pmid: 10090733
references.citation: J Mol Biol. 1997 May 2;268(2):331-47
references.pmid: 9159474
references.citation: J Mol Biol. 1995 Feb 10;246(1):194-208
references.pmid: 7853397
references.citation: J Biomol Struct Dyn. 2003 Feb;20(4):487-506
references.pmid: 12529149
references.citation: Nucleic Acids Res. 1986 Feb 25;14(4):1801-9
references.pmid: 3951996
references.citation: J Mol Biol. 1988 Jul 5;202(1):139-55
references.pmid: 2845094
references.citation: J Mol Biol. 1973 Aug 5;78(2):301-19
references.pmid: 4747633
references.citation: Radiat Res. 2004 Dec;162(6):604-15
references.pmid: 15548110
references.citation: Nucleic Acids Res. 1985 Sep 11;13(17):6375-86
references.pmid: 4047943
references.citation: J Mol Biol. 2002 May 24;319(1):191-207
references.pmid: 12051946
references.citation: Nucleic Acids Res. 2002 Mar 15;30(6):1371-8
references.pmid: 11884635
references.citation: Nucleic Acids Res. 2002 May 15;30(10):2183-92
references.pmid: 12000838
references.citation: Biochemistry. 1987 Jun 30;26(13):4068-75
references.pmid: 3651437
references.citation: Nucleic Acids Res. 1992 Apr 25;20(8):1933-41
references.pmid: 1579495
references.citation: Biochem Biophys Res Commun. 1972 Jun 28;47(6):1504-9
references.pmid: 5040245
references.citation: J Mol Biol. 1989 Jan 20;205(2):437-47
references.pmid: 2538629
references.citation: Proc Natl Acad Sci U S A. 1988 Sep;85(17):6332-6
references.pmid: 3413099
references.citation: Eur J Biochem. 1995 Mar 1;228(2):279-90
references.pmid: 7705340
references.citation: Biopolymers. 1992 Jul;32(7):783-94
references.pmid: 1391631
references.citation: Biochemistry. 1993 Apr 13;32(14):3583-95
references.pmid: 8385483
references.citation: Radiat Res. 1993 May;134(2):160-9
references.pmid: 7683818
references.citation: Nucleic Acids Res. 1985 May 10;13(9):3111-29
references.pmid: 2987873
references.citation: J Biomol Struct Dyn. 1989 Feb;6(4):655-67
references.pmid: 2619933
references.citation: Nature. 1985 Jun 13-19;315(6020):604-6
references.pmid: 4010774
references.citation: J Biomol Struct Dyn. 1990 Apr;7(5):1095-115
references.pmid: 2361001
references.citation: Annu Rev Biophys Biomol Struct. 1997;26:629-58
references.pmid: 9241432