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

We present a new algorithm for identifying molecules that display a pharmacophore, or in general a structural motif, by efficiently constructing and screening huge virtual combinatorial libraries of diverse compounds. The uniqueness of this algorithm is its ability to build and screen libraries of ca. 10(18) 3D molecular conformations within a reasonable time scale, thereby increasing the chemical space that can be virtually screened by many orders of magnitude. The algorithm may be used to design new molecules that display 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.