Cellular respiration, a common topic among introductory and cellular biology curricula, is a complex biological process that exemplifies core biological concepts, including systems, pathways and transformation of energy, and structure and function relationships. Unfortunately, many students struggle to understand cellular respiration and its associated concepts. To help students with their understanding of cellular respiration, we developed a lesson that uses computational modeling and simulations through an on-line modeling platform, Cell Collective (learn.cellcollective.org). Computational models and simulations allow students to observe and influence the dynamics of complex biological systems not observable in static diagrams from textbooks. In our lesson, students explore different aspects of cellular respiration by making changes to the system. For each perturbation, students investigate the underlying mechanistic causes by iteratively predicting the mechanism, testing their prediction with simulations, interpreting and reporting on their findings, and reflecting upon their prediction until they can accurately describe the underlying mechanism. Because the lesson is self-contained and requires little guidance from the teacher, the lesson can be implemented in a wide-variety of settings without the need for many changes to existing curricula.