In collaboration with Prof. Yang Qu (UNB), we are studying the biosynthetic machinery that allows plants to produce pharmaceutically important monoterpene indole alkaloids (MIAs) such as vinblastine (anticancer) and ajmaline (antiarrhythmic). Experimental studies by the Qu group have revealed several genes that, through molecular biology and phylogenetic analysis, should encode enzymes involved in the biosynthetic cascade that produces MIAs. Our research group develops 3D models of these enzymes through homology modeling and machine learning methods. Molecular docking experiments are then carried out on these protein models to assess their substrate binding and converting capabilities. The computational studies serve to corroborate experimental results and to unravel the complete biosynthesis pathway of important MIAs.
Current projects:
- We have studied N-methyltransferase enzymes, producing 3D models, docking their coenzyme (S-adenosylmethionine, SAM) and docking a series of putative substrates. https://doi.org/10.3389/fpls.2024.1451298
- We have studied cytochrome P450 monooxygenase enzymes, producing 3D models, including their iron-heme prosthetic group, and docking a series of putative substrates to determine substrate selectivity.
https://doi.org/10.1101/2024.07.29.605674