Models have been developed that allow the biological activity of a DNA segment to be altered in a desired direction. Partial least squares projections to latent structures (PLS) was used to establish a quantitative model between a numerical description of 68 bp fragments of 25 E.coli promoters and their corresponding quantitative measure of in vivo strength. This quantitative sequence-activity model (QSAM) was used to generate two 68 bp fragments predicted to be more potent promoters than any of those on which the model originally was based. The optimized structures were experimentally verified to be strong promoters in vivo.