Software for Interactive Analysis of Large Molecular Assemblies

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Software for Interactive Analysis of Large Molecular Assemblies

Tom Goddard, Conrad Huang, and Thomas E. Ferrin;

Resource for Biocomputing, Visualization, and Informatics
University of California, San Francisco

Over the past five years, we have developed, documented, and distributed several novel software tools for our Chimera visualization package for use in the interactive analysis of large molecular assemblies. Examples of large assemblies are viruses, ribosomes, actin and myosin filaments, and chromosomes. These analysis tools address two important areas in structural biology: the analysis of medium and low resolution density maps determined by electron microscopy (EM), and the analysis of atomic models comprising tens to thousands of macromolecules. Some of the tools we have developed allow fitting atomic resolution models obtained by crystallography into EM density maps, extracting regions of density maps along molecular boundaries, and examining contacts between neighboring protein and nucleic acid molecules in atomic models of large assemblies. This core research project will develop additional useful and novel interactive analysis tools to advance the study of molecular assemblies, a rapidly growing area of structural biology.

Our technological research and development efforts in this area began five years ago with the proposal of a core project entitled "Volume visualization for analyzing cellular systems at multiple resolutions." We have now renamed this project to "Software for Interactive Analysis of Large Molecular Assemblies" because we believe it to be more descriptive. Our specific goals for this project are to:
Develop improved capabilities for the display and manipulation of atomic models comprised of tens to thousands of macromolecules.

Develop methods for creating animations of assemblies such as virus capsids and ribosomes that elucidate structural organization and conformational changes.

Develop methods for the display and analysis of medium and low resolution density maps intended primarily for researchers studying molecular assemblies using electron microscopy single particle reconstruction.

Develop methods for the analysis of structurally heterogeneous assemblies, for example chromosomes or polymorphic viruses such as HIV, imaged by electron microscope tomography.

Figure caption: Myosin thick filament density map (Woodhead, 2005) fit using a smooth muscle myosin crystal structure (PDB 1i84) containing two heavy chains, two essential light chains, and two regulatory light chains. Copies of the myosin subunit are automatically reoriented to maintain helical symmetry during fitting so that steric clashes are apparent.

References:

Goddard TD, Huang CC, Ferrin TE. Visualizing density maps with UCSF Chimera. J Struct Biol. 2006 Jul 15; [Epub ahead of print]
Goddard TD, Huang CC, Ferrin TE. Software extensions to UCSF chimera for interactive visualization of large molecular assemblies. Structure. 2005 Mar;13(3):473-82.
Woodhead JL, Zhao FQ, Craig R, Egelman EH, Alamo L, Padron R. Atomic model of a myosin filament in the relaxed state. Nature 2005, 436(7054):1195-1199.