Combinatorial chemistry and high-throughput screening are revolutionizing the process of lead discovery in the pharmaceutical industry. Large numbers of structures and vast quantities of biological assay data are quickly being accumulated, overwhelming traditional structure/activity relationship (SAR) analysis technologies. Recursive partitioning is a method for statistically determining rules that classify objects into similar categories or, in this case, structures into groups of molecules with similar potencies. SCAM is a computer program implemented to make extremely efficient use of this methodology. Depending on the size of the data set, rules explaining biological data can be determined interactively. An example data set of 1650 monoamine oxidase inhibitors exemplifies the method, yielding substructural rules and leading to general classifications of these inhibitors. The method scales linearly with the number of descriptors, so hundreds of thousands of structures can be analyzed utilizing thousands to millions of molecular descriptors. There are currently no methods to deal with statistical analysis problems of this size. An important aspect of this analysis is the ability to deal with mixtures, i.e., identify SAR rules for classes of compounds in the same data set that might be binding in different ways. Most current quantitative structure/activity relationship methods require that the compounds follow a single mechanism. Advantages and limitations of this methodology are presented.

MOLGEN is a computer program system which is designed for generating molecular graphs fast, redundancy free and exhaustively. In the present paper we describe its basic features, new features of the current release MOLGEN 3.5, and future developments which provide considerable improvements and extensions. 1 Introduction MOLGEN [1--7] is a generator for molecular graphs (=connectivity isomers or constitutional formulae) allowing to generate all isomers that correspond to a given molecular formula and (optional) further conditions like prescribed and forbidden substructures, ring sizes etc. The input consists of ffl the empirical formula, together with ffl an optional list of macroatoms, which means prescribed substructures that must not overlap, ffl an optional goodlist, that consists of prescribed substructures which may overlap, ffl an optional badlist, containing forbidden substructures, ffl an optional interval for the minimal and maximal size of rings, ffl an optional num...