Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Untangling a protein’s influences

09.01.2012
A computational strategy that reveals how environmental interactions affect protein shape could steer more sophisticated approaches to drug design

Most proteins have multiple moving parts that rearrange into different conformations to execute particular functions. Such changes may be induced by molecules in the immediate environment, including water and similar solvents as well as other molecules or drugs that a protein might encounter.


Figure 1: DIPA reveals shifts in protein conformation that arise from the strengthening or weakening effects of perturbing protein–water interactions. The bars along the bottom indicate the relative strength of the perturbations (weak, left; strong, right).
Copyright : 2011 Yohei M. Koyama

A new computational approach devised by Yohei Koyama and Hiroki Ueda at the RIKEN Quantitative Biology Center, Kobe, and Tetsuya Kobayashi of the University of Tokyo now provides researchers with the means to understand how specific interactions between environmental molecules and a given protein facilitate particular conformational rearrangements1.

In the past, researchers have focused on the movement of specific atomic coordinates, using a statistical tool called principal component analysis (PCA) to identify segments of the protein that collectively contribute to a given rearrangement. However, such approaches simply map a protein’s movements rather than clarifying interactions that contribute to those changes. To address this limitation, Koyama, Ueda and Kobayashi developed a method called distance-dependent intermolecular perturbation analysis (DIPA), which uses PCA to characterize how subsets of environmental molecules contribute to conformational shifts.

“Perturbation analysis is a method to understand complex systems by observing responses to changes in the system,” explains Koyama. “For example, to understand the function of a machine without a manual, we sometimes manipulate the controls and observe its response.” Accordingly, DIPA simulates the manipulation of different environmental molecules and determines whether they favor particular conformational states for a protein (Fig. 1).

The researchers initially used DIPA to simulate the influence of surrounding water on a chemically capped version of the amino acid alanine and identified three conformational states. In a subsequent analysis, they used a larger molecule called chignolin, a hairpin-shaped polypeptide containing ten amino acids, and observed four states and the environmental influences that stabilize those states. “We observed that molecular states can be identified clearly in terms of intermolecular protein–water interactions,” says Koyama.

DIPA is a powerful tool, but the researchers cannot yet apply it to the movements of full-sized proteins, as existing computational hardware is inadequate for such demanding molecular dynamics simulations. “Current simulations are performed over timescales of a few microseconds,” says Koyama, “but many proteins manifest their functions over an order of many microseconds or even milliseconds.” However, supercomputing initiatives underway at RIKEN—such as the ultra-fast ‘K computer’ slated for completion in 2012—could help bring these capabilities within reach, at which point DIPA promises to become a potent resource for the rational design of protein-specific drugs.

The corresponding author for this highlight is based at the Laboratory for Synthetic Biology, RIKEN Quantitative Biology Center

gro-pr | Research asia research news
Further information:
http://www.riken.jp
http://www.researchsea.com

Further reports about: DIPA PCa RIKEN amino acid quantitative synthetic biology

More articles from Life Sciences:

nachricht Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

nachricht Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Research reveals how order first appears in liquid crystals

23.05.2018 | Life Sciences

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

NIST puts the optical microscope under the microscope to achieve atomic accuracy

23.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>