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 The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

nachricht How protein islands form
15.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

Im Focus: Scientists improve forecast of increasing hazard on Ecuadorian volcano

Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).

The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New thruster design increases efficiency for future spaceflight

16.08.2017 | Physics and Astronomy

Transporting spin: A graphene and boron nitride heterostructure creates large spin signals

16.08.2017 | Materials Sciences

A new method for the 3-D printing of living tissues

16.08.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>