Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Lost in a crowd

29.03.2010
Introducing additional complexity to a simulation gives researchers better insight into how cellular signaling networks might operate

One of the biggest challenges in simulating biological processes is developing mathematical models that accurately reflect the dynamics of real molecules.

Koichi Takahashi, of the RIKEN Advanced Science Institute in Yokohama, is in a position to know—as a founding member of the E-Cell Project, he and his colleagues have spent the last 14 years working towards development of a comprehensive simulation of a whole functioning cell.

Takahashi’s work has focused on dynamic behavior of populations of signaling factors. Such analyses are typically based on ‘mean-field’ descriptions, which assume an essentially averaged distribution of molecules throughout the cellular volume. This shortcut overlooks a lot of real-world complexity, but is made necessary by the excessive computational demands of more accurate models.

Things have now changed, thanks to a breakthrough from Pieter Rein ten Wolde at AMOLF in the Netherlands, whose team developed an algorithm called Green’s Function Reaction Dynamics (GFRD) that enables sophisticated single-particle-level simulations with considerably reduced computing power1. Together, Takahashi and ten Wolde developed a faster and more accurate version of GFRD, and applied it to mitogen-activated protein kinase (MAPK) cascades, a type of signaling pathway associated with diverse functions in the eukaryotic cell2.

MAPK signaling is a multi-stage process; at each step, one kinase enzyme activates another, downstream kinase through two sequential chemical modifications. Predictions from mean-field-based simulations of MAPK dynamics have depended heavily on whether the enzyme is assumed to act ‘processively’, introducing both modifications without releasing the substrate, or ‘distributively’, releasing the substrate after each modification.

However, Takahashi and ten Wolde found strikingly different results with their model, which introduces the possibility of re-binding—a scenario in which substrates receive their second modification from the same enzyme that introduced the first. For example, slow diffusion of enzymes and substrate within the cytosol could lead to much more rapid overall activation kinetics by keeping substrates within easy reach of their upstream kinases. “‘Walking slower’ can speed up the response of the system,” says Takahashi. This is the opposite of mean-field model predictions, and essentially erases the distinction between distributive and processive in this context.

These data demonstrate the importance of increasing complexity in models, a direction in which the authors are continuing to move. “We are extending our method so that we can also include structures such as membranes and organelles,” says Takahashi. “We are also working to make the method even more high-performance, because that will enable us to represent intracellular molecular crowding.”

The corresponding author for this highlight is based at the Biochemical Simulation Research Team, RIKEN Advanced Science Institute.

Journal information

1. van Zon, J.S. & ten Wolde, P.R. Simulating biochemical networks at the particle level and in time and space: Green’s function reaction dynamics. Physical Review Letters 94, 128103 (2005).

2. Takahashi, K., Tãnase-Nicola, S. & ten Wolde, P.R. Spatio-temporal correlations can drastically change the response of a MAPK pathway. Proceedings of the National Academy of Sciences USA 107, 2473–2478 (2010).

Saeko Okada | Research asia research news
Further information:
http://www.rikenresearch.riken.jp/eng/research/6226
http://www.researchsea.com

More articles from Life Sciences:

nachricht Are there sustainable solutions in dealing with dwindling phosphorus resources?
16.10.2017 | Leibniz-Institut für Nutzierbiologie (FBN)

nachricht Strange undertakings: ant queens bury dead to prevent disease
13.10.2017 | Institute of Science and Technology Austria

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

Im Focus: New nanomaterial can extract hydrogen fuel from seawater

Hybrid material converts more sunlight and can weather seawater's harsh conditions

It's possible to produce hydrogen to power fuel cells by extracting the gas from seawater, but the electricity required to do it makes the process costly. UCF...

Im Focus: Small collisions make big impact on Mercury's thin atmosphere

Mercury, our smallest planetary neighbor, has very little to call an atmosphere, but it does have a strange weather pattern: morning micro-meteor showers.

Recent modeling along with previously published results from NASA's MESSENGER spacecraft -- short for Mercury Surface, Space Environment, Geochemistry and...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

Conference Week RRR2017 on Renewable Resources from Wet and Rewetted Peatlands

28.09.2017 | Event News

 
Latest News

A single photon reveals quantum entanglement of 16 million atoms

16.10.2017 | Physics and Astronomy

The melting ice makes the sea around Greenland less saline

16.10.2017 | Earth Sciences

On the generation of solar spicules and Alfvenic waves

16.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>