ABSTRACT
High resolution crystallography of drug-Deoxyribonucleic acid (DNA) complexes with short-defined oligonucleotides, biophysical and biochemical DNA binding studies, and computer modeling complement each other in providing a comprehensive picture of DNA interactions. Interaction of small molecules with DNA can involve covalent bonding to DNA or non-covalent binding in the grooves or insertion between the base-pairs of DNA. The most detailed structural information about intercalation comes from X-ray crystal structure determination of DNA-intercalator complexes, involving simple oligonucleotides of defined sequence. Crystal structures of dinucleoside-intercalator complexes have provided conformational details of intercalation at the atomic level. Two alternative approaches that complement X-ray crystallography are biochemical techniques and computer graphics. Among the various biochemical techniques, footprinting methodology provides high resolution information about preferred DNA-ligand binding sites. Computer graphics are being used increasingly in studying ligand receptor binding. A major advantage of the method is that it enables rapid visualization of drug-DNA interactions.
