Identification of novel bacterial RNA polymerase 'Switch Region' inhibitors using pharmacophore model based on multi-template and similarity research

摘要

Bacterial RNA polymerase, which is a complex molecular machine for RNA synthesis in all cellular organisms, appears to be a new discovered and potential protein. Switch Region of bacterial RNA polymerase turns out to be an ideal target for antibiotics in consequence of highly conserved in gram-positiveegative bacterial and non-conserved in human RNAP. Present study collected recently discovered bacterial RNAP inhibitors and generated a pharmacophore query in combination with similarity research for new antibiotics identification. The generated query is consisted of three features: one hydrophobic site and two acceptor atoms. Then, pharmacophore and similarity research as two different strategies were used against to 1,623,646 compounds from ZINC database. Finally, ten compounds were filtered out as potential antibiotics. This work could be less limitation in various scaffold research and more accuracy in antibiotics discovery by applying novel inhibitors.