Proteins are essential to life and play central roles in medicine, biotechnology, and sustainable manufacturing. They enable critical chemical reactions that support human health, environmental processes, and industrial production. However, improving protein function remains a major challenge because current approaches often rely on trial-and-error methods or static structural information, which do not fully capture how proteins carry out complex chemical transformations. In particular, there is limited understanding of how energy flows from the solvent into proteins to enable and regulate their activity. This project seeks to uncover how energy flow governs protein function, providing a new foundation for designing more efficient and versatile enzymes. By advancing fundamental knowledge of protein energy distribution, this research will support innovation in areas such as therapeutic protein development, environmental remediation, and sustainable biomanufacturing, thereby contributing to national priorities in scientific progress, economic competitiveness, and public welfare. The project also integrates research and education through a comprehensive training and outreach plan. This includes hands-on K–12 workshops that connect basic science concepts to real-world applications, mentored research opportunities for community college students to broaden participation in science and engineering, and curriculum development that incorporates active research into undergraduate and graduate education. Together, these efforts will help build a diverse and highly skilled workforce while increasing public understanding of how molecular science contributes to societal challenges. This project will establish a quantitative biophysical framework that links intramolecular energy flow to enzyme function. The central hypothesis is that energy redistribution following ligand binding is not uniform but instead propagates through specific structural pathways that regulate catalytic