As Proof-of-Principle, Model Provides Insight into HIV Structure
Researchers can now explore viruses, bacteria and components of the human body in more detail than ever before with software developed at The Scripps Research Institute (TSRI).
In a study published online ahead of print December 1 by the journal Nature Methods, the researchers demonstrated how the software, called cellPACK, can be used to model viruses such as HIV.
“We hope to ultimately increase scientists’ ability to target any disease,” said Art Olson, professor and Anderson Research Chair at TSRI who is senior author of the new study.
Putting cellPACK to the Test
The cellPACK software solves a major problem in structural biology. Although scientists have developed techniques to study relatively large structures, such as cells, and very small structures, such as proteins, it has been harder to visualize structures in the medium “mesoscale” range.
With cellPACK, researchers can quickly and efficiently process the data they’ve collected on smaller structures to assemble models in this mid-size range. Previously, researchers had to create these models by hand, which took weeks or months compared with just hours in cellPACK.
As a demonstration of the software’s power, the authors of the new study created a model of HIV showing how outer “spike” proteins are distributed on the surface of the immature virus.
The new model put to the test a conclusion made by HIV researchers from super-resolution microscopic studies—that the distribution of the spike proteins on the surface of the immature virus is random. But by using cellPACK to generate thousands of models, testing alternative hypotheses, the researchers found that the distribution was not random. “We demonstrated that their interpretation of the distribution did not match that hypothesis,” said Olson.
A Team Effort
The cellPACK software began as the thesis project of a TSRI graduate student, Graham Johnson, now a QB3 faculty fellow at the University of California, San Francisco (UCSF) who continues to contribute to the project. Johnson had more 15 years’ experience as a medical illustrator, and he wanted to create an easy way to visualize mesoscale structures. cellPACK is an expansion of Johnson’s autoPACK software, which maps out the density of materials—from concrete in a building to red blood cells in an artery.
The researchers see cellPACK as a community effort, and they have made the autoPACK and cellPACK software free and open source. Thousands of people have already downloaded the software from http://www.autopack.org .
“With the creation of cellPACK, Dr. Olson and his colleagues have addressed the challenge of integrating biological data from different sources and across multiple scales into virtual models that can simulate biologically relevant molecular interactions within a cell,” said Veersamy Ravichandran, PhD, of the National Institutes of Health's National Institute of General Medical Sciences, which partially funded the research. “This user-friendly tool provides a new platform for data analysis and simulation in a collaborative manner between laboratories.”
As new information comes in from the scientific community, researchers will tweak the software so it can model new shapes. “Making it open source makes it more powerful,” said Olson. “The software right now is usable and very useful, but it’s really a tool for the future.”
In addition to Olson and Johnson, other authors of the study, “cellPACK: A Virtual Mesoscope to Model and Visualize Structural Systems Biology,” are Ludovic Autin, Mostafa Al-Alusi, David S. Goodsell and Michel F. Sanner, all of TSRI. For more information, see http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.3204.html
This study was supported by the National Science Foundation (NSF 07576), Autodesk, the National Institutes of Health (P41 GM103426 and P50GM103368), the California Institute for Quantitative Biosciences and a UCSF School of Pharmacy 2013 Mary Anne Koda-Kimble Seed Award for Innovation.
About The Scripps Research Institute
The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including two Nobel laureates—work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu .
Office of Communications
Madeline McCurry-Schmidt | EurekAlert!
Molecular evolution: How the building blocks of life may form in space
26.04.2018 | American Institute of Physics
Multifunctional bacterial microswimmer able to deliver cargo and destroy itself
26.04.2018 | Max-Planck-Institut für Intelligente Systeme
Magnetic resonance imaging, or MRI, is a widely used medical tool for taking pictures of the insides of our body. One way to make MRI scans easier to read is...
At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.
Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...
Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.
Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
26.04.2018 | Power and Electrical Engineering
26.04.2018 | Life Sciences
26.04.2018 | Power and Electrical Engineering