2022 Undergraduate Summer Research Program Participant

Home Department: Bioengineering
Mentor: Soichi Wakatsuki (Photon Science Directorate and Structural Biology)

“Development of a Mutant Photoactivatable Active Site for Time-Resolved Crystallography”

The aim of this research is to collect information on structural dynamics from time-resolved, serial femtosecond (factor of 10−15) crystallography (SFX) to elucidate how the protein, 3CLpro, the main protein degrading enzyme (protease) found in coronaviruses, distinguishes between viral and host-cell substrates. To achieve this requires first, designing, synthesizing and crystallizing photoactivatable SARS-COV2 3CLPro by incorporating caged-cysteines at its active functional sites. Second, establishing protocols for activating the protease in crystals for time resolved SFX. The above steps use laser excitation and pump-and-probe X-ray Free Electron Laser SFX (XFEL-SFX) to elucidate protein dynamics of the protease in complex with human protein substrates. These steps all lead to performing complete, multimodal, time-resolved experiments which will help elucidate the structural and functional dynamics of a key protein involved in SARS-COV2 pathogenesis.