Abstract
A computerized linked-atom modeling system was developed to examine the stereochemical requirements for intercalation of planar drugs into DNA. All classes of conformational possibilities for extending the polynucleotide backbone were examined for their ability to accommodate insertion of a drug into a base-paired region of DNA compatible with adjacent regions of B-DNA while stacking interactions, steric strain and non-bonded interatomic contacts were optimised. One conformation was found which proved superior to all others in ability to satisfy these criteria: an extension of the backbone by characteristic changes in two torsion angles to trans values, plus a change in one sugar puckering to C3'-endo to relieve strain in an adjacent residue. The turn angle distributed over three polynucleotides for this most general mode of intercalation is 90 degrees, equivalent to a helical unwinding of -18 degrees for B-DNA.