MULTI-SCALE VISUALIZATION OF LARGE MOLECULAR COMPLEXES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We are developing software extensions to the UCSF Chimera molecular modeling package (http://www.cgl.ucsf.edu/chimera) for interactive visualization and analysis of large molecular assemblies such as viruses and ribosomes. These extensions facilitate studying atomic resolution models over a range of scales from atomic detail, to secondary structure (helices and sheets), to tertiary structure (protein and nucleic acid folds), to quaternary structure (packing of macromolecules to form an assembly). While many computer programs permit interactive exploration of small sets of protein or nucleic acid macromolecules, none work well with assemblies of 30 or more molecules. Known virus particle structures are composed of hundreds to thousands of molecules and are particularly difficult to study with existing software. The software we've developed focus on the quaternary structure level. The basic capabilities are encapsulated in the Multiscale Models tool. It allows representing molecules as simple surfaces that show overall molecular shape. This abstraction is needed for systems having hundreds of molecules. Applying symmetry is another basic capability. Most of the approximately 250 virus capsid structure have icosahedral symmetry. Only the asymmetric unit (1/60 of the capsid) is specified in atomic coordinate files. We are able to use the symmetry to display the entire capsid while only creating copies of the atomic coordinates when they are needed for displaying asymmetric units with differing styles and colorings. This is important for virus capsids which can contain millions atoms. In addition to abstract representations and symmetry handling, another challenge posed by large assemblies is in navigating to relevant subassemblies. For example, a virus capsid may have two layers each comprised of hundreds of proteins. A mechanism is needed to hide the outer layer so that the inner layer can be studied. Subassemblies such as virus capsid layers are in general not annotated in the Protein Databank files so defining these subassemblies is left to the user. Our multiscale extension permits navigating to subassemblies using user-defined molecule groupings. Details of the Multiscale Models tool were published in Goddard TD, Huang CC, Ferrin TE. Software extensions to UCSF chimera for interactive visualization of large molecular assemblies. Structure (Camb). 2005 Mar;13(3):473-82. More advanced capabilites added in past years include an efficient algorithm for calculating atomic contacts between molecular components, the ability to show crystallographic unit cells, the ability to delete components, the ability to show transparent surfaces in combination with other molecular display styles, and ability to export 3 dimensional models for making animations. These capabilities have been used to create images for Virus Particle Explorer web site (http://viperdb.scripps.edu/) for all known icosahedral virus capsid structures.