It is now possible to approach the structural modeling and visualization of entire cells with detail at the atomic level. In this project, we will expand the capabilities of cellPACK, a method for creating integrative 3D models of cellular environments, bridging from the level of atoms to the level of cells. These models will provide unprecedented possibilities for the understanding of cellular function and disease states, enabling new opportunities for intervention. They will also challenge several aspects of the technologies needed to generate, visualize and interactively explore very large 3D and 4D structural datasets. Our goal is to develop the modeling and visualization tools that enable others to develop, run and analyze dynamic simulations of these complex models. Several critical barriers must be overcome to make this effort a successful tool for research and scientific education, including the management of large informational databases, methods for the automated modeling of the structure and interaction of soluble, fibrous, and membrane-bound molecular assemblies in crowded cellular environments, and comprehensible visualization of, and interaction with these large and heterogenous models. We will approach these challenges with four specific aims: 1) Procedural methods for mesoscale modeling of complex assemblies, such as the bacterial nucleoid, peptidoglycan, lipopolysaccharide, and polysomes; 2) Computer-assisted tools for the management of complex multiscale data for specifying 3D mesoscale models of cells; 3) Development of fast and effective methods to allow display of and interaction with these complex mesoscale models; 4) Application of these methods to research in bacterial biology and creation of a Google Earth inspired viewer for use in education and outreach.
CellPACK combines information from cellular ultrastructure, genomics and proteomics, and atomic structure to build three-dimensional models of subcellular environments at molecular detail. In the proposed work, we will bring cellPACK technology and the associated visualization tool cellVIEW to a new level with an ambitious goal: the modeling and visualization of an entire bacterial cell. The methods will be applied in two settings: as a tool for research in the study of Escherichia coli structure and function, and in educational settings as a way to promote understanding of structure and function of living cells.
| Goodsell, David S; Autin, Ludovic; Olson, Arthur J (2018) Lattice Models of Bacterial Nucleoids. J Phys Chem B 122:5441-5447 |
| Goodsell, David S; Jenkinson, Jodie (2018) Molecular Illustration in Research and Education: Past, Present, and Future. J Mol Biol 430:3969-3981 |
| Klein, Tobias; Autin, Ludovic; Kozlikova, Barbora et al. (2018) Instant Construction and Visualization of Crowded Biological Environments. IEEE Trans Vis Comput Graph 24:862-872 |
| Goodsell, David S; Franzen, Margaret A; Herman, Tim (2018) From Atoms to Cells: Using Mesoscale Landscapes to Construct Visual Narratives. J Mol Biol 430:3954-3968 |
