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 for interactively analyzing 3-dimensional density maps obtained by electron microscopy (EM). The analysis aims to determine structures and inner workings of molecular machines such as viruses, ribosomes, microtubules and motors, muscle filaments, and dozens of others systems that are targets of current research. It is believed that most proteins in living organisms are parts of large molecular assemblies. Advances in experimental methods in the past several years have greatly accelerated research on these systems. The primary database of EM density maps (www.ebi.ac.uk/msd-srv/emsearch/index.html) was founded in 2002 and now (2010) has 773 entries. Software for deducing structures from these maps is being actively developed by many labs. Our software displays contour surfaces of density maps. Maps from electron microscopy have resolutions in the 5 - 100 Angstrom range which is too coarse to see atomic detail. Analysis involves fitting known atomic structures from crystallography into the maps, identifying structures in maps corresponding to unidentified proteins, and comparing maps of the same system under different experimental conditions to deduce conformational changes or binding of ligands or specific macromolecules. Our software tools, which are part of the UCSF Chimera molecular modeling package, support fitting, carving out density regions, coloring maps, and building coarse models in maps. In the past we have added the ability to slice maps along an arbitrarily oriented and movable plane displaying density values on the cut surface.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001081-34
Application #
8363597
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
$16,768
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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