A fast algorithm for searching for molecules containing a pharmacophore invery large virtual combinatorial libraries

We present a new algorithm for identifying molecules that display a pharmac ophore, or in general a structural motif, by efficiently constructing and s creening huge virtual combinatorial libraries of diverse compounds. The uni queness of this algorithm is its ability to build and screen libraries of c a. 10(18) 3D molecular conformations within a reasonable time scale, thereb y increasing the chemical space that can be virtually screened by many orde rs of magnitude. The algorithm may be used to design new molecules that dis play a desired pharmacophore on predefined sets of chemical scaffolds. This is demonstrated herein by screening a library of backbone cyclic peptides to find candidate peptido- and proteinomimetics.