This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.We are developing software extensions to the UCSF Chimera molecularmodeling package (www.cgl.ucsf.edu/chimera) for interactivevisualization and analysis of large molecular assemblies such asviruses and ribosomes. These extensions facilitate studying atomicresolution models over a range of scales from atomic detail, tosecondary structure (helices and sheets), to tertiary structure(protein and nucleic acid folds), to quaternary structure (packing ofmacromolecules to form an assembly). While many computer programspermit interative exploration of small sets of protein or nucleic acidmacromolecules, none work well with assemblies of 30 or moremolecules. Known virus particle structures are composed of hundredsto thousands of molecules and are particularly difficult to study withexisting 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 overallmolecular shape. This abstraction is needed for systems havinghundreds of molecules. Applying symmetry is another basic capability.Most of the approximately 250 virus capsid structure have icosahedralsymmetry. Only the asymmetric unit (1/60 of the capsid) is specifiedin atomic coordinate files. We are able to use the symmetry todisplay the entire capsid while only creating copies of the atomiccoordinates when they are needed for displaying asymmetric units withdiffering styles and colorings. This is important for virus capsidswhich can contain millions atoms. In addition to abstractrepresentations and symmetry handling, another challenge posed bylarge assemblies is in navigating to relevant subassemblies. Forexample, a virus capsid may have two layers each comprised of hundredsof proteins. A mechanism is needed to hide the outer layer so thatthe inner layer can be studied. Subassemblies such as virus capsidlayers are in general not annotated in the Protein Databank files sodefining these subassemblies is left to the user. Our multiscaleextension permits navigating to subassemblies using user-definedmolecule groupings.Details of the Multiscale Models tool were published in Goddard TD,Huang CC, Ferrin TE. Software extensions to UCSF chimera forinteractive visualization of large molecular assemblies. Structure(Camb). 2005 Mar;13(3):473-82.More advanced capabilites added in past years include an efficientalgorithm for calculating atomic contacts between molecularcomponents, the ability to show crystallographic unit cells, theability to delete components, the ability to show transparent surfacesin combination with other molecular display styles, and ability toexport 3 dimensional models for making animations.These capabilities have been used to create images for Virus ParticleExplorer web site (http://viperdb.scripps.edu/) for all knownicosahedral virus capsid structures. A tutorial presenting the basiccapabilities(www.cgl.ucsf.edu/chimera/tutorials/virus-howto/showvirus.html)was used to train 80 participants at the Single ParticleReconstructions and Visualization workshop at the National Center forMacromolecular Imaging, and 40 participants at a Chimera trainingworkshop at UC Irvine, both in 2005.
Showing the most recent 10 out of 508 publications
