SPROUT - A PROGRAM FOR STRUCTURE GENERATION

SPROUT is a new computer program for constrained structure generation that is designed to generate molecules for a range of applications in molecular recognition. It uses artificial intelligence techniques to m oderate the combinatorial explosion that is inherent in structure gene ration. The program is presented here for the design of enzyme inhibit ors. Structure generation is divided into two phases: (i) primary stru cture generation to produce molecular graphs to fit the steric constra ints; and (ii) secondary structure generation which is the process of introducing appropriate functionality to the graphs to produce molecul es that satisfy the secondary constraints, e.g., electrostatics and hy drophobicity. Primary structure generation has been tested on two enzy me receptor sites; the p-amidino-phenyl-pyruvate binding site of tryps in and the acetyl pepstatin binding site of HIV-1 protease. The progra m successfully generates structures that resemble known substrates and , more importantly, the predictive power of the program has been demon strated by its ability to suggest novel structures.