Energetics of intercalation specificity. I. Backbone unwinding

An empirical partitioned‐potential function with optimized parameters was employed to investigate the basis of intercalation specificity recently observed by experimental techniques. The nature of this specificity is discussed in terms of component interactions for all non‐truncated complementary dinucleoside triphosphate mini‐ (or miniature) helices. Our calculations agree with available evidence indicating the preference of Pyr(3′‐5′)Pur sequences over Pur(3′‐5′)Pyr sequences to change from the B‐DNA to the intercalated conformation. Base–base (stacking) and base–phosphate interactions control the specificity. The extent of net electrostatic charge on the phosphate groups play an important but limited role in establishing the observed specificity. These results should apply for the class of aromatic agents involved in nonspecific intercalation with nucleic acids but not necessarily for aromatic agents involved in specific reactions with a particular nucleotide base.