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 (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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001081-34
Application #
8363584
Study Section
Special Emphasis Panel (ZRG1-BST-D (40))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
34
Fiscal Year
2011
Total Cost
$27,938
Indirect Cost
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Viswanath, Shruthi; Chemmama, Ilan E; Cimermancic, Peter et al. (2017) Assessing Exhaustiveness of Stochastic Sampling for Integrative Modeling of Macromolecular Structures. Biophys J 113:2344-2353
Chu, Shidong; Zhou, Guangyan; Gochin, Miriam (2017) Evaluation of ligand-based NMR screening methods to characterize small molecule binding to HIV-1 glycoprotein-41. Org Biomol Chem 15:5210-5219
Portioli, Corinne; Bovi, Michele; Benati, Donatella et al. (2017) Novel functionalization strategies of polymeric nanoparticles as carriers for brain medications. J Biomed Mater Res A 105:847-858
Nguyen, Hai Dang; Yadav, Tribhuwan; Giri, Sumanprava et al. (2017) Functions of Replication Protein A as a Sensor of R Loops and a Regulator of RNaseH1. Mol Cell 65:832-847.e4
Alamo, Lorenzo; Koubassova, Natalia; Pinto, Antonio et al. (2017) Lessons from a tarantula: new insights into muscle thick filament and myosin interacting-heads motif structure and function. Biophys Rev 9:461-480
Sofiyev, Vladimir; Kaur, Hardeep; Snyder, Beth A et al. (2017) Enhanced potency of bivalent small molecule gp41 inhibitors. Bioorg Med Chem 25:408-420
Parsonage, Derek; Sheng, Fang; Hirata, Ken et al. (2016) X-ray structures of thioredoxin and thioredoxin reductase from Entamoeba histolytica and prevailing hypothesis of the mechanism of Auranofin action. J Struct Biol 194:180-90
Nekouzadeh, Ali; Rudy, Yoram (2016) Conformational changes of an ion-channel during gating and emerging electrophysiologic properties: Application of a computational approach to cardiac Kv7.1. Prog Biophys Mol Biol 120:18-27
Forman, Stuart A; Miller, Keith W (2016) Mapping General Anesthetic Sites in Heteromeric ?-Aminobutyric Acid Type A Receptors Reveals a Potential For Targeting Receptor Subtypes. Anesth Analg 123:1263-1273
Sathyanarayana, Bangalore K; Li, Peng; Lin, Jian-Xin et al. (2016) Molecular Models of STAT5A Tetramers Complexed to DNA Predict Relative Genome-Wide Frequencies of the Spacing between the Two Dimer Binding Motifs of the Tetramer Binding Sites. PLoS One 11:e0160339

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