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 The Secret of the Rock Drawings
24.05.2019 | Max-Planck-Institut für Chemie

nachricht Chemical juggling with three particles
24.05.2019 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New studies increase confidence in NASA's measure of Earth's temperature

A new assessment of NASA's record of global temperatures revealed that the agency's estimate of Earth's long-term temperature rise in recent decades is accurate to within less than a tenth of a degree Fahrenheit, providing confidence that past and future research is correctly capturing rising surface temperatures.

The most complete assessment ever of statistical uncertainty within the GISS Surface Temperature Analysis (GISTEMP) data product shows that the annual values...

Im Focus: The geometry of an electron determined for the first time

Physicists at the University of Basel are able to show for the first time how a single electron looks in an artificial atom. A newly developed method enables them to show the probability of an electron being present in a space. This allows improved control of electron spins, which could serve as the smallest information unit in a future quantum computer. The experiments were published in Physical Review Letters and the related theory in Physical Review B.

The spin of an electron is a promising candidate for use as the smallest information unit (qubit) of a quantum computer. Controlling and switching this spin or...

Im Focus: Self-repairing batteries

UTokyo engineers develop a way to create high-capacity long-life batteries

Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...

Im Focus: Quantum Cloud Computing with Self-Check

With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.

Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...

Im Focus: Accelerating quantum technologies with materials processing at the atomic scale

'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.

However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

On Mars, sands shift to a different drum

24.05.2019 | Physics and Astronomy

Piedmont Atlanta first in Georgia to offer new minimally invasive treatment for emphysema

24.05.2019 | Medical Engineering

Chemical juggling with three particles

24.05.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>