Software for Interactive Analysis of Large Molecular Assemblies

Tom Goddard
November 13, 2006


Illustrating the Problem

From Tim Baker talk, Large Biomolecular Complexes Visualization workshop, September 2005. Color PBCV-1 virus map to illustrate symmetry.

Ten computer programs needed -- several in-house utilities (RobEM, pif*), Situs, O, and Chimera.

"I do not know if I make myself clear, probably not. It is really a kind of complex procedure."

Solution and Vision

Project Vision

Our goal is to expand Chimera capabilities to encompass the common interactive visualization and analysis tasks in the study of large molecular assemblies involving atomic models and electron microscopy maps.

We will continue our leading and highly unique role developing interactive software to supplant the patchwork of programs borrowed from other disciplines in current use for exploring large assemblies.

Keywords: System integration. Highly collaborative work. Same-day prototyping. Multiple length scales. Real-time data exploration. User interface. Documentation. Thousands of users. Desktop computing.

Not the Vision: Long-running computations. Special-purpose algorithmic code. Software for specialized hardware (computing clusters, volumetric rendering boards, ...).

Current Chimera Standing

EM Databases

The two public EM databases use Chimera as their primary visualization tool, and link to Chimera web site on each of their data set web pages.

Gallery of EMDB entries

September 2005.

Example VIPERdb web page

Chimera Extensions from Chiu Lab

Labs can develop Chimera plugins to meet specialized needs, building on existing Chimera capabilities.

Example: 25 Chimera plugins developed by the National Center for Macromolecular Imaging and distributed with EMAN. User interfaces shown below.

  • Fitting (5 tools)
  • Secondary structure search (4)
  • Segmentation (5)
  • Map filtering (2)
  • Vibrational mode viewer
  • Animation (2)
  • EMAN interface
  • Measuring Stick
  • Surface coloring
  • File conversion (3)

Other Software

Chimera is the only widely distributed interactive analysis program focused on large assemblies and electron microscopy.

Each lab uses many software packages because none encompass basic EM map and model capabilities.

Volume visualization packages, commercial, targeting diverse fields medical imaging, earth sciences, oil/gas resevoirs, aerospace engineering, financial modeling, .... Have very limited molecular model capabilities.

Molecular modeling packages. Have limited density map capabilities or specialized for atomic resolution crystallographic maps.

In-house EM map packages. Inadequate EM lab resources to develop and distribute program for wide base of users.

Summary of Proposed Developments

Require a range of map and model analysis capabilities focused on the organization of molecular assemblies beyond the atomic level: arrangements of molecules, domains, and secondary structure elements, their mechanisms of assembly and conformational rearrangements.

Large Atomic Models

Animating Assemblies

Single Particle EM Maps

Structurally Heterogeneous Assemblies (primarily EM Tomography)

Chimera Demonstrations

HIV Spike EM Tomography

June 2006 EM tomography example fitting HIV gp120/gp41 spikes using Chimera. Spikes recognize target cells and initiate viral fusion. Illustrates combined use of tomography and structure averaging approach.

Zhu P, Liu J, Bess J Jr, Chertova E, Lifson JD, Grise H, Ofek GA, Taylor KA, Roux KH.
Distribution and three-dimensional structure of AIDS virus envelope spikes.
Nature. 2006 Jun 15;441(7095):847-52. Epub 2006 May 24.

John Sedat Collaboration, EM Tomography

September 2006 chromosome EM tomography poster from Sedat lab. Chimera used for modeling helical structure.

Manfred Auer Collaboration, EM Tomography

Recent poster showing EM tomography of haircell molecular mechanical linkers. Chimera used to model unknown linkers and fit candidate molecules.

Progress since June 2006

Example Chimera scripts and commands developed for collaborators since June 2006 grant submission. These are plugins distributed separately from Chimera on our experimental features web page.

Collaborations Initiated from Workshops and Conferences

Many collaborations outside UCSF have been established by attending meetings and giving talks. Here are examples from the past year.

Collaborations with Public Databases

Collaborations with public archives are important for success of Chimera and the databases. Omitted collaborations with EMDB and VIPERdb public electron microscopy databases from grant proposal.

Core Project Aims

Broad aims of large assemblies core project listed in our June 2006 grant proposal.

Develop advanced capabilities for: