Nuevolution′s Chemetics technol. allows the synthesis of ultra-large libraries (10exp8-10exp14 small mols.) and the subsequent isolation of NCE′s by a selection process mimicking natural evolution. As such, Chemetics promises to revolutionize drug discovery. Chemetics is a wet chem. approach enabling DNA-directed, one-pot synthesis and screening of billions of small drug-like mols. in weeks. A huge library of small organic mols. is generated in one tube through the combination of Drug Fragments, wherein each Drug Fragment has been encoded by DNA. The overall outcome of the Chemetics encoding is a small organic mol. attached to the DNA that encodes it. The library of small mol.-DNA complexes generated above can be exposed to an affinity chromatog. column to which a target of interest has been immobilized. Ligands bind the target; those small mols. that do not bind are washed off the column. The ligands are now eluted and the small mol. ligands can then be amplified, by first amplification of the DNA by PCR, and then Chemetics encoding. Alternatively, their structure may be revealed through the sequencing of their DNA. Overall, the Chemetics technol. will allow the isolation and identification of the higher affinity, small mol. ligands in the huge library.