Understanding the cell: Future views of structural biology Martin Beck, Roberto Covino, Inga Hänelt, and Michaela Müller-McNicoll review the current state and future directions of structural biology in the context of cellular function. They highlight the limitations of current structural biology approaches, which often focus on static, isolated macromolecular structures, and emphasize the need for a more dynamic, integrated view of cellular processes. The authors argue that structural biology should move toward a 4D virtual reality of cells using digital twins, which can capture molecular details, dynamic changes, and enable simulations of molecular processes. This approach would allow for experimentally testable predictions and a deeper understanding of how cells function. Structural biology has made significant progress in elucidating the structures of many macromolecular machines at high resolution. However, challenges remain in understanding the dynamic nature of biomolecules and the complex interactions that govern cellular function. Many biomolecules are inherently dynamic, and their conformational ensembles are crucial for their function. Traditional structural biology techniques often fail to capture these dynamics, leading to an incomplete understanding of cellular processes. The authors also discuss the limitations of the reductionist approach in understanding complex systems. They reference P. Anderson's "More is different," which highlights that new properties and effective laws emerge in complex systems that are difficult to predict from their fundamental description. This challenges the assumption that knowing the structure of individual molecules is sufficient to understand their function in a cellular context. The authors emphasize the importance of integrating structural and cellular biology, biophysics, and computational sciences to better understand cellular self-organization. They discuss the role of local confinement, molecular rulers, and self-organization mechanisms of membranes in cellular function. They also highlight the importance of understanding the dynamic nature of lipid composition and membrane organization in cellular processes. The authors argue that future structural cell biology should focus on dynamic, integrated models that capture the complexity of cellular processes. They suggest that combining in vitro and in situ data, along with advanced imaging and omics techniques, will be essential for understanding molecular activities inside cells. They also emphasize the need for new theoretical concepts and frameworks that capture dynamics and complexity in cellular systems. In conclusion, the authors argue that structural biology must move beyond static, isolated structures to a more dynamic, integrated view of cellular processes. This will require new technologies, theoretical concepts, and interdisciplinary approaches to better understand how cells function.Understanding the cell: Future views of structural biology Martin Beck, Roberto Covino, Inga Hänelt, and Michaela Müller-McNicoll review the current state and future directions of structural biology in the context of cellular function. They highlight the limitations of current structural biology approaches, which often focus on static, isolated macromolecular structures, and emphasize the need for a more dynamic, integrated view of cellular processes. The authors argue that structural biology should move toward a 4D virtual reality of cells using digital twins, which can capture molecular details, dynamic changes, and enable simulations of molecular processes. This approach would allow for experimentally testable predictions and a deeper understanding of how cells function. Structural biology has made significant progress in elucidating the structures of many macromolecular machines at high resolution. However, challenges remain in understanding the dynamic nature of biomolecules and the complex interactions that govern cellular function. Many biomolecules are inherently dynamic, and their conformational ensembles are crucial for their function. Traditional structural biology techniques often fail to capture these dynamics, leading to an incomplete understanding of cellular processes. The authors also discuss the limitations of the reductionist approach in understanding complex systems. They reference P. Anderson's "More is different," which highlights that new properties and effective laws emerge in complex systems that are difficult to predict from their fundamental description. This challenges the assumption that knowing the structure of individual molecules is sufficient to understand their function in a cellular context. The authors emphasize the importance of integrating structural and cellular biology, biophysics, and computational sciences to better understand cellular self-organization. They discuss the role of local confinement, molecular rulers, and self-organization mechanisms of membranes in cellular function. They also highlight the importance of understanding the dynamic nature of lipid composition and membrane organization in cellular processes. The authors argue that future structural cell biology should focus on dynamic, integrated models that capture the complexity of cellular processes. They suggest that combining in vitro and in situ data, along with advanced imaging and omics techniques, will be essential for understanding molecular activities inside cells. They also emphasize the need for new theoretical concepts and frameworks that capture dynamics and complexity in cellular systems. In conclusion, the authors argue that structural biology must move beyond static, isolated structures to a more dynamic, integrated view of cellular processes. This will require new technologies, theoretical concepts, and interdisciplinary approaches to better understand how cells function.