Multidisciplinary drug discovery research model involving six chemistry department faculty members and two dozen undergraduate students will be described. The model integrates molecular biology, protein expression and purification, enzymology, NMR-based compound screening and characterization, medicinal chemistry, and parasitology into a project team similar to those in the pharmaceutical industry. The team’s long term goal is to discover novel therapies against <i>Trichomonas vaginalis</i>, the most prevalent non-viral sexually transmitted infection. Two essential nucleoside ribohydrolase enzymes were cloned, expressed, purified, and characterized enzymatically. One is selective for purines, the other for pyrimidines. Both enzymes were screened against a 2,000-compound fragment library to identify ligand-efficient scaffolds to enable medicinal chemistry. Undergraduate students work together on all facets of the project. Students in the molecular biology and protein labs prepare enzyme for use in the NMR-based activity assays, and also characterize compounds synthesized in the medicinal chemistry labs. Students in the NMR lab carry out fragment screens and characterize compounds synthesized by the medicinal chemistry labs. Students in the medicinal chemistry labs design and synthesize compounds using active structures identified by the NMR group, and then send their newly-synthesized compounds back to the protein, NMR, and parasitology labs for testing. A project team Moodle page is used as a central data and literature repository. Students in one lab interact with students in the other labs on a regular basis -- reagents and compounds are often handed directly from one student to another. The entire project team, including faculty and students, meets on a regular basis. Students benefit from being integrated into broader aspects of chemistry, but each student also has a clear ownership stake in the project that is determined by their lab discipline and enzyme. This allows them to write hypothesis-driven honors theses as well as to create individual presentations for national conferences.

Multidisciplinary drug discovery research model at an undergraduate institution

2019 Spring National Meeting

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