The design, implementation, and capabilities of an extensible visualization system, UCSF Chimera, are discussed. Chimera is segmented into a core that provides basic services and visualization, and extensions that provide most higher level functionality. This architecture ensures that the extension mechanism satisfies the demands of outside developers who wish to incorporate new features. Two unusual extensions are presented: Multiscale, which adds the ability to visualize large-scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales. Other extensions include Multalign Viewer, for showing multiple sequence alignments and associated structures; ViewDock, for screening docked ligand orientations; Movie, for replaying molecular dynamics trajectories; and Volume Viewer, for display and analysis of volumetric data. A discussion of the usage of Chimera in real-world situations is given, along with anticipated future directions. Chimera includes full user documentation, is free to academic and nonprofit users, and is available for Microsoft Windows, Linux, Apple Mac OS X, SGI IRIX, and HP Tru64 Unix from http://www.cgl.ucsf.edu/chimera/.

/pdf/ucsf-chimera-a-visualization-system-for-exploratory-research-59xu54fhxg.pdf

UCSF Chimera--a visualization system for exploratory research and analysis.

Rapid growth in nanotechnology is increasing the likelihood of engineered nanomaterials coming into contact with humans and the environment. Nanoparticles interacting with proteins, membranes, cells, DNA and organelles establish a series of nanoparticle/biological interfaces that depend on colloidal forces as well as dynamic biophysicochemical interactions. These interactions lead to the formation of protein coronas, particle wrapping, intracellular uptake and biocatalytic processes that could have biocompatible or bioadverse outcomes. For their part, the biomolecules may induce phase transformations, free energy releases, restructuring and dissolution at the nanomaterial surface. Probing these various interfaces allows the development of predictive relationships between structure and activity that are determined by nanomaterial properties such as size, shape, surface chemistry, roughness and surface coatings. This knowledge is important from the perspective of safe use of nanomaterials.

Understanding biophysicochemical interactions at the nano–bio interface

BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

RELION: implementation of a Bayesian approach to cryo-EM structure determination.

Single-particle electron cryomicroscopy (cryo-EM) is a powerful method for determining the structures of biological macromolecules. With automated microscopes, cryo-EM data can often be obtained in a few days. However, processing cryo-EM image data to reveal heterogeneity in the protein structure and to refine 3D maps to high resolution frequently becomes a severe bottleneck, requiring expert intervention, prior structural knowledge, and weeks of calculations on expensive computer clusters. Here we show that stochastic gradient descent (SGD) and branch-and-bound maximum likelihood optimization algorithms permit the major steps in cryo-EM structure determination to be performed in hours or minutes on an inexpensive desktop computer. Furthermore, SGD with Bayesian marginalization allows ab initio 3D classification, enabling automated analysis and discovery of unexpected structures without bias from a reference map. These algorithms are combined in a user-friendly computer program named cryoSPARC (http://www.cryosparc.com).

cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination

Drug Delivery: Vaults Engineered for Hydrophobic Drug Delivery (Small 10/2011)

Tuberculosis-causing mycobacteria have thick cell-wall and capsule layers that are formed from complex structures. Protein secretion across these barriers depends on a specialized protein secretion system, but none has been reported. We show that Mycobacterium tuberculosis Rv3705c and its homologous MSMEG_6251 in Mycobacterium smegmatis are tube-forming proteins in the mycobacterial envelope (TiME). Crystallographic and cryo-EM structures of these two proteins show that both proteins form rotationally symmetric rings. Two layers of TiME rings pack together in a tail-to-tail manner into a ring-shaped complex, which, in turn, stacks together to form tubes. M. smegmatis TiME was detected mainly in the cell wall and capsule. Knocking out the TiME gene markedly decreased the amount of secreted protein in the M. smegmatis culture medium, and expression of this gene in knocked-out strain partially restored the level of secreted protein. Our structure and functional data thus suggest that TiME forms a protein transport tube across the mycobacterial outer envelope.

/pdf/identification-and-architecture-of-a-putative-secretion-tube-p3u7te35x0.pdf

Identification and architecture of a putative secretion tube across mycobacterial outer envelope.

Structure of LARP7 Protein p65-telomerase RNA Complex in Telomerase Revealed by Cryo-EM and NMR.

Nature 496, 187–192 (2013); doi:101038/nature12062 Owing to an editorial oversight, accession numbers for the negative-stain electron microscopy maps for this Article were not obtained The electron microscopy maps have been deposited in the Electron Microscopy Data Bank (http://emdatabankorg) forall of the structures shown in the main text and in the Supplementary figures

/pdf/corrigendum-the-architecture-of-tetrahymena-telomerase-euwaqcxig1.pdf

Corrigendum: The architecture of Tetrahymena telomerase holoenzyme

Deregulation of mini-chromosome maintenance (MCM) proteins are associated with genomic instability and cellular abnormality. MCM complexes are recruited to replication origins for S phase genome duplication. Paradoxically, MCM proteins are expressed in large number of origins and are associated with unreplicated chromatin regions away from the origins during G1 and S phases. We report an unusually wide left-handed filament structure for an archeal MCM, as determined by X-ray and electron microscopy. The crystal structure reveals that an α-helix bundle formed between two neighboring subunits plays a critical role in filament formation which we show through mutation and electron microscopy. The filament interior has a remarkably strong electro-positive surface spiraling along the inner filament channel which we establish as the binding site for double-stranded DNA. We find that MCM filament binding to DNA causes dramatic topological changes which negatively supercoil circular DNA through inducing loosening ...

Z. Hong Zhou

Papers

Drug Delivery: Vaults Engineered for Hydrophobic Drug Delivery (Small 10/2011)

Identification and architecture of a putative secretion tube across mycobacterial outer envelope.

Structure of LARP7 Protein p65-telomerase RNA Complex in Telomerase Revealed by Cryo-EM and NMR.

Corrigendum: The architecture of Tetrahymena telomerase holoenzyme

123 Mini-chromosome maintenance complexes form a filament to remodel DNA structure and topology