This research objective to investigate the interaction between the bacterium E. coli with the components of the ethanol extract of herbs as a chemical library (a collection of various chemical compounds) on the nature of biological materials in the province of Papua. E. coli as a target is one of the model organisms used in new drug development (drug discovery) in this study. This model is also consistent with the research of the human genome in an effort to balance the new strategy in the diagnosis, treatment, and prevention of disease. The interaction was investigated by growing the bacteria on solid media containing ethanol extracts of herbs, herbal ethanol extract encounters with bacterial chromosomal DNA by dot blotting method and the results observed by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). On the growth of bacteria on solid media containing fungi, bacteria continue to grow so that interaction can not be observed directly, while the method of TLC increased value retention factor (Rf) of ethanol extract of herbs before and after the interaction with DNA. For the eluent composition of methanol : water (6:4), the ethanol extract of herbs that have not diinteraksikan have Rf of 0.84 increased to 0.94 after DNA interactions. The results of the HPLC analysis provides more detailed information about the interactions that occurred with a reduction in height and broad peak at a retention time of 2.67; 12.8; and 16.9 min. This most likely indicates an interaction between the molecules of DNA with the compounds contained in the ethanol extracts of herbs.