Abstract: A method for determining the relationship of chemical structure to biological activity based on the topology and physiochemical properties of "cavities" or "artificial constructs" constructed from molecular models of nucleic acids, including, double-stranded DNA, double-stranded RNA and double-stranded DNA-RNA complexes. With DNA models, the second codon base is removed from each of the sixty-four possible codon-anticodon complexes in the configuration of DNA to form the cavities. Cavities were also formed between the base pairs of partially uncoiled DNA. Using the conventional physiochemical principles of hydrogen bonding and steric constraints, molecules having varying types of biological activity will fit stereochemically into certain cavities while, conversely, molecules which do not form complementary fits into a given cavity will not possess the respective biological activity. Also, the method can be utilized to determine the degree of biological activity of compounds.