Prokaryotic viruses (phages) are the most abundant organisms on earth. Studies of Nobel laureates Max Delbrück, Salvador Luria, Alfred Hershey and Francois Jacob on T4 and λ phages laid foundations for molecular biology and modern genetics. Phage studies not only help to broaden our fundamental research but are important in microbial ecosystems from our gut to the oceans, help to combat antibiotic resistance and unlock biotechnological applications. For successful phage applications we need to know how they function. Despite almost a century of phage studies and their importance, functions of 83% of prokaryotic virus protein families remain unknown.
Development of the AlphaFold2 – an Artificial Intelligence (AI)-based tool for structure prediction, revolutionized structural biology and made it possible to obtain a protein structure the quality of which can be on par with the experimental structures. Moreover, AI-based protein language models are becoming the fundamental part of state-of-art bioinformatics software for protein functional annotation.
Here, we propose to use AI tools for characterization of prokaryotic virus proteins. We expect to find novel protein families and characterize them by prioritizing nucleic acids binding proteins, due to their potential for translational applications in the regulation and modification of nucleic acids. Most intriguing proteins will be subjected to experimental studies and cryoEM analysis.