Mapping the functional surface of the ribosome exit tunnel with novel antibiotics: a combined approach using computational design, chemo-biosynthesis, and experimental characterization
Chaitan Khosla (Chemistry)
Vijay Pande (Chemistry)
Jody Puglisi (Structural Biology)

The ribosome plays a key role in the central dogma of biology: it is the biological machine which synthesizes proteins (translation).  Due to this key role biologically, the ribosome also plays a key biomedical role, as a natural target for antibiotics.  In this proposal, we seek to develop novel small molecule inhibitors of translation by combing novel synthetic methods to push the chemical diversity of compounds, novel computational methods to do initial screens of possibly viable compounds, followed by cutting edge experimental assays of binding to the ribosome.  Moreover, by using computational and experimental methods to describe ribosome binding of a family of related antibiotics, we will begin to probe the dynamic nature and chemical landscape the ribosome exit tunnel.