An algorithm for optimal design of chemical structures from molecular fragments

An approach to molecular design is suggested, The procedure involves three main steps: forming a basic set of compounds possessing the given property; dividing the molecular graphs (MG) of these compounds into fragments; cons tructing a MG in which the environment of fragments is similar to that in b asic compounds. Optimality of an MG is defined in terms of the properties o f substituents which are relevant to molecular recognition (lipophilicity, molar refraction, etc.). An effective algorithm is developed for design of MG with an optimal environment of each submolecule. An example is given of compound design from the structural fragments of several nucleoside inhibit ors of the inverse transcriptase of HIV-1. Using this algorithm provides a compromise between the similarity and diversity of chemical structures with in the given set of compounds.