DNA, hydrogen bonding

Figure 7.7 Color codes for the recognition patterns at the edges of the base pairs in the major (a) and minor (b) grooves of B-DNA. Hydrogen-bond acceptors are red hydrogen-bond donors are blue. The methyl group of thymine is yellow, while the corresponding H atom of cytosine is white.

Netropsin lying in the minor groove of B-DNA hydrogen-bonded to bases in the central ATAT tetranucleotide. From Coll et al,r... 

Hydrogen bonds are only rarely an issue in the modeling of small metal complexes. There are, however, some cases where hydrogen bonds are particularly important. For example, when diamineplatinum(II) complexes bind to DNA, hydrogen bonds form between the H(amine) atoms and oxygen atoms on the DNA, and these interactions may be very important in determining the sequence specificity of Pt/DNA interactions[140]. Also, interactions between cationic and anionic complexes will inevitably involve hydrogen bonds and these terms will probably determine whether there is substantial stereoselectivity in the interactions. 

DNA is a duplex molecule in which two polynucleotide chains (or strands) are linked to one another through specific base pairing (Fig. 7-1). Adenine in one strand is paired to thymine in the other, and guanine is paired to cytosine. The two chains are said to be complementary. This was one of the essential features of Watson and Crick s proposal regarding the structure of DNA. Hydrogen bonds form between the opposing bases within a pair. In the structure proposed by Watson and Crick, A T and G C base pairs are roughly planar, with H bonds (dotted lines), as shown in Fig. 7-1. Note that two H bonds form in an A T pair and three in a G C pair. 

In double-stranded DNA, hydrogen bonding between the bases on the two strands typically occurs between ... 

Figure 10. Netropsin (1) bound to the minor groove of DNA. Hydrogen bonds are shown in yellow, while bonds are color-coded by atom type netropsin carbon = white, DNA carbon = purple, nitrogen = blue, oxygen = red, phosphorus = yellow.

DNA. Since polylysine binds preferentially to AT-rich DNA, hydrogen bonding in addition to salt bridge formation is likely to occur. Complex formation between polylysine or polycytosine is also reversible and may lead to rod-like structures (Haynes et al., 1970). Small cationic peptides with an aromatic amino acid, e.g., the tripeptide Lys-Tep.Lys, first add to double-stranded DNA and then force the aromatic side chain to intercalate between two nucleic base pairs. Bending of the DNA is then observed (Gabbay et al., 1973). 

Figure 4.7. Representations of some unusual higher order DNA structures triple helix (triplex), in which a third DNA strand hydrogen-bonds in the major groove of a double-stranded DNA a hairpin, in which a single strand of DNA hydrogen-bonds with itself to make a stem and nonpaired bases are pushed out to form a loop a tetraplex (quadruplex), in which (in this case) a single strand of DNA folds over on itself in an unusual G-G-G-G hydrogen bonding pattern, important in telomeric structure at the ends of chromosomes and a Holliday junction, in which four single strands of DNA base pair as usual but form this unusual complex structure, believed to be a good model for DNA recombination.

InteracUon between molecules Polypeptide chains form interchain hydrogen bonds. So do the two stands of DNA. Hydrogen bonds have been studied very profitably using infrared spectroscopy. 

Figure 9.5 The structure of DNA - hydrogen bonding between bases and coiling of the chains to form the double helix.

For all forms of DNA, hydrogen bonding between the two spiral chains stabilizes the double helix. Replication of DNA occurs when the hydrogen bonds are broken, and the two strands are separated. These form the templates that are used to make identical copies, via enzymes called DNA polymerases. In fact, the second strand of the double helix is complementary to the first, it contains no extra information but is involved in replication. Ribonucleic acid (RNA) is also found in cells. It has a similar structure to DNA, but the sugar is instead D-ribose and uracil bases replace thymine bases. RNA is important in the synthesis of proteins. It is produced from DNA templates via the process of transcription. Further details of protein biochemistry can be found elsewhere (e.g. Voet and Voet, 1995). Here we simply emphasize that life itself is created from that special class of soft material called polymers. 

An useful step made in this study was to compare 15 energy minimised structures, selected initially from the dynamics trajectory at 10 ps intervals. Pairwise RMSD values between these structures varied between 1.3 A and 1.9 A. (over the backbone atoms of headpiece and the operator, excluding the terminal base-pairs). All the structures were rather similar and acceptable from both stereochemical and NMR points of view. It was nevertheless found that several different protein-DNA hydrogen bonding arrangements were possible and could not be discriminated on the basis of the conformational energy. 

A second simulation carried out one year later [80] appeared to vindicate partly this idea, since the inclusion of 30 counterions reduced overall DNA bending to 19°. This simulation concerned the ER protein dimer interacting with the consensus dimer sequence ERE-ERE or with a mixed GRE-ERE site. The results indicated that binding specificity and stability are conferred by a network of both direct and water mediated protein-DNA hydrogen bonds. With the consensus sequence, this network involves three water molecules, the residues Glu 25, Lys 28, Lys 32 and Arg 33 and several DNA bases. In the nonconsensus sequence, a fluctuating network of hydrogen bonds allows water molecules to enter the protein-DNA interface and two additional waters are located at the interface. The authors also noted that the interaction of the protein with the DNA backbone is weaker with the consensus site than with the non-... 

---