RUI: Prebiotic origins of biological energy (PrOBE)

Adelphi University, Garden City NY

Investigators

Abstract

Small peptides containing only a limited set of 20 cellular amino acids were most likely responsible for biological energy generation at the origin of cellular life. These prebiotic peptides or small proteins then evolved into the complex and specialized proteins that generate energy for cells today. This project aims to identify peptides that may have played a role in energy generation when life on earth was beginning; these peptides might reveal a signature of emerging life on earth and elsewhere. This project will immerse a group of undergraduate students and high school students into cutting-edge scientific research. Students will receive hands-on experience using state-of-the-art equipment at Adelphi University and sophisticated instrumentation located at Rutgers University. Biological energy required at the origin of life most likely involved a transition from inorganic electron transfer, catalyzed by geochemical surfaces, to organic electron transfer catalyzed by small peptides. These prebiotic electron transfer peptides or small proteins then evolved into the specialized electron transfer proteins that provide the energy source of extant life. For this to be the case, peptides or small proteins composed only of amino acids available under prebiotic conditions must be capable of catalyzing electron transfer reactions. This project will use artificial intelligence deep learning algorithms in combination with experimental validation to discover prebiotic oxidoreductases composed only of amino acids that were available to prebiotic chemistry. Extant ferredoxin, Rossmann-like and flavodoxin folds will be redesigned composed of only prebiotic amino acids. The novel designs will be synthesized, or expressed and purified, and then characterized for structure by circular dichroism and nuclear magnetic resonance spectroscopy, and for function by electron paramagnetic resonance spectroscopy and cyclic voltammetry. This approach will identify plausible, prebiotic chemical entities that could have served as scaffolds for the origin of biological FeS cluster-mediated or flavin-mediated electron transfer. Demonstrating that designed prebiotic peptides or proteins have similar folds and electron transfer functions as their extant, parent proteins would provide compelling support for the hypothesis that these prebiotic polypeptides played a role in the origin of life. The project will also advance the development and application of generative artificial intelligence methods to understand protein design and protein evolution. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.