Decoding enzymes and beyond: Advances in Enzyme Research, Computational Tools, and the Future of Molecular Science
Jiří Damborský is a professor of biochemistry and head of the Loschmidt Laboratories at the Faculty of Science, Masaryk University in the Czech Republic. His interest in protein engineering was sparked when he “entered” the protein structure using stereo glasses for the first time. “It was in 1993, and I was blown away by the beauty of protein structures. Believe it or not, this was in Groningen during my visit to the laboratories of Professor Dick Janssen and Professor Herman Berendsen. We became long-life friends with Dick. I am incredibly grateful for his support and friendship. Guess the name of this protein :-),” Jiri remembers.
Prof. Damborský leads a dynamic group that researches enzyme mechanisms and evolution, focusing on dehalogenases and luciferases. The scope extends beyond enzymes, with a commitment to developing experimentally validated software tools and microfluidic technologies for protein science. In the biomedical field, the team aims to decipher the structural basis of Alzheimer's Disease and pioneer new treatments for acute stroke.
Reflecting on the evolution of computational tools, Prof. Damborský acknowledges the contributions of software to improve accuracy of predictions such as Rosetta, FOLDX, AlphaFold, ProteinMPNN, and RF Diffusion, etc. Some of these methods could not have been developed without the dedicated work of thousands of structural biologists, who patiently solved structures of proteins to atomistic accuracy, one by one. Acknowledged should also be bioinformaticians, who developed high-quality databases and maintained infrastructure for data storage and retrieval. The symbiotic relationship between experimental and computational approaches has paved the way for high-impact developments that continue to shape the field.
A suite of computational tools and databases, crafted by Prof. Damborský research group is accessible through the Protein Engineering Portal (https://loschmidt.chemi.muni.cz/portal/). “We have several ongoing projects that will lead to the release of experimentally validated tools: AggreProt to eliminate aggregation-prone regions, TmProt to estimate melting temperature from primary sequence, PPIformer to design mutations for protein-protein interactions, CaverDock 2.0 to study ligand passage via flexible tunnels using robotics, and FireProt 3.0 to eliminate destabilising mutations using machine learning. We have exciting collaborations with the partners from Prague, Ostrava and Austin.”
The conversation doesn't end with tools; it extends into the realm of foresight. Jiri shares an optimistic perspective on the future trajectory of computational tools, artificial intelligence (AI), and machine learning (ML) in enzyme redesign. "In the years to come, these models will not only be accurate but faster and more user-friendly. Our mission is to contribute by developing in-house models, such as SoluProt, TmProt, AggreProt, PPIformer, and integrating critically validated third-party models. The goal is to make the complex world of molecular design accessible to all," expresses Prof. Damborsky. Beyond the laboratory, the commitment to knowledge dissemination stands tall. The team aims to nurture the next generation of molecular scientists – Hands-on Computational Enzyme Design courses (https://loschmidt.chemi.muni.cz/academy) guide protein and metabolic engineers through the intricate world of computational tools and enzyme design.
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