Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Computers spot shape clues

19.10.2001


Computer power is unravelling complex proteins.
© SPL


Two techniques may help deduce proteins’ functions.

Imagine trying to guess what machines do just be looking at them. Even a can-opener would pose problems, if you didn’t know about cans. This is the challenge that faces molecular biologists as they try to make sense of protein molecules in the cell.

Two new techniques may help. One deduces a protein’s function from its shape; the other deduces its shape from a list of component parts1,2.



Having read most of the human genome, researchers can, in principle, deduce a protein’s sequence - the chain of amino-acid building blocks of which it is made. In a functioning protein, this chain folds up in a particular three-dimensional way.

The first step in understanding a protein’s job is therefore to work out its shape. Predicting protein folding is, on the face of it, an enormous challenge. Most proteins contain dozens or hundreds of amino acids, so there is an astronomical number of ways in which these might be arranged into a compact, folded structure.

Fortunately, only a tiny fraction of these folds - perhaps a thousand - are found in natural proteins. The challenge is to deduce the best fit of a particular protein sequence to one of these folds. This is called the protein-threading problem.

Traditionally, the problem is tackled by assuming that each amino acid prefers to be surrounded by others of a specific kind, and then to look for the best compromise between the needs of all the amino acids. Success using this approach depends on how well we know what the amino acids prefer.

Instead of trying to deduce this from physical and chemical principles, Jayanth Banavar of Pennsylvania State University and colleagues use a set of known protein structures to train a computer program to recognize the preferences of each amino acid. Once trained, the program, a neural network, can then predict unknown structures.

This learning-based method is more successful than one based on a priori assumptions about amino-acid preferences, the researchers show. The network correctly predicted the structures of 190 out of 213 test proteins; the conventional approach got only 137 structures right.

Site construction

The next stage of the problem, going from structure to function, is what Mary Jo Ondrechen of Northeastern University in Boston, Massachusetts, and colleagues have looked at2. Most proteins are enzymes - they facilitate a chemical reaction. The priority of function hunters is to find the region where this transformation takes place, called the active site.

Many amino-acid groups in proteins can act as acids or bases - they can accept or release hydrogen ions. Usually this take-up or release is fairly abrupt as the acidity (pH) of the protein solution is altered - the amino acid switches from having the ion attached to being free of it over a narrow pH range.

Ondrechen’s team have found that amino acids at active sites don’t act in this simple way. Here, the behaviour of one unit affects that of the others.

A computer program that uses the known structure to predict how each amino acid in the protein sheds or acquires hydrogen ions when the pH is changed can spot this different behaviour of amino acids at active sites.

Anomalous behaviour, say the researchers, doesn’t necessarily indicate that an amino acid lies at the active site. But several such units close together are almost certainly indicators of the active site. The team says that their method could be automated to identify active sites rapidly - hopefully transforming a suite of protein structures into a list of their functions.


References

  1. Chang, I., Cieplak, M., Dima, R. I., Maritan, A. Banavar, J. R. Protein threading by learning. Proceedings of the National Academy of Sciences USA, in the press (2001).

  2. Ondrechen, M. J., Clifton, J. G. & Ringe, D. THEMATICS : a simple computational predictor of enzyme function from structure. Proceedings of the National Academy of Sciences USA, 98, 12473 - 2478, (2001).


PHILIP BALL | Nature News Service
Further information:
http://www.nature.com/nsu/011025/011025-1.html
http://www.nature.com/nsu/

More articles from Life Sciences:

nachricht Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society

nachricht 127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>