Featured Research

from universities, journals, and other organizations

Sometimes the average just isn't good enough: Averaging not always best for analying protein crystal structures

February 10, 2014
University of Vienna
Computational biologists show that averaging is not always a good thing when it comes to analyzing protein crystal structures. Their recent work shows that protein structures could be more dynamic and heterogeneous than current methods of X-ray analysis suggest.

This is an atomistic model of the protein villin headpiece. Color and the size of ellipsoids capture the local dynamics of individual atoms.
Credit: Copyright: Bojan Zagrovic

Usually averaging is a good thing that can make life a lot easier. For example, when you eat out with a group of friends and it comes to paying. If everyone had a meal and a drink and you split the bill total by the number of people, everyone will pay pretty close to what they would have paid for their individual meal and drink. However, if some people had a starter, a steak for main, a dessert and champagne while you had spaghetti and a soft drink, you will feel pretty much ripped off when you pay the average of 45€ for your meal. In science, averaging is a good thing too -- researchers often repeat their experiment several times and average the results. As long as the results are within a certain level of deviation, the scientists can then be confident that what they found in the lab is reliable.

Related Articles

Determining protein structures: X-ray crystallography

One of the most important methods in biology is X-ray crystallography, which is used to analyze protein structures. Knowing such structures allows scientists to draw conclusions about what a protein does and how it does it, but also to develop medicines that inhibit or activate that protein's function. For X-ray crystallography, proteins are purified and dried to form a crystal, each of which contains millions of copies of the same protein. Shining X-rays on the crystal then allows conclusions about where the smallest building blocks of a protein -- the atoms -- are located and how dynamic each of them is, i.e. how much it can wiggle around in its location. By doing that for one crystal they get averages, which are based on the behavior of millions of copies of equivalent atoms. You would think this is enough to be confident that this is what the protein looks like in nature too. But it's actually not and sometimes averaging can be misleading as Bojan Zagrovic, lead author of the study, explains: "Take, for example, the average location of a goalie during a football match. Considering that the teams switch sides at halftime, it is roughly at the center of the field, a clearly non-representative situation."

Atoms in proteins wiggle up to six fold more than currently thought

So how correctly do current programs for the analysis of X-ray crystallographic data capture a protein's structure and its dynamics? This was one of the questions Antonija Kuzmanic wanted to answer during her PhD studies with Zagrovic and supported by his European Research Council (ERC) Starting Grant. Together with collaborator Navraj S. Pannu of Leiden University, The Netherlands, she used computer simulation to "built" a protein crystal and analyzed it by the methods of X-ray crystallography, before using standard software programs to capture the protein's features from crystallographic data. This allowed her to test if the way crystallographic data is currently analyzed "sees" what's really there. "We were really surprised to find that current software programs, used to predict a protein's structure from X-ray crystallography data, underestimates the level of dynamics -- so how much each atom can wiggle around in its position -- by up to six fold. This is a lot, it's like if we could suddenly turn our head 180 degrees rather than just to the left or right," Antonija Kuzmanic explains.

Inspirational work

Garib Murshudov of the University of Cambridge, UK, structural biologist and one of the examiners of Antonija Kuzmanic's PhD thesis, wrote: "This is my favorite chapter, it is inspirational … it clearly shows that it is necessary to design new ways to describe protein dynamics in crystals." More accurate ways to interpret X-ray crystallography data and determine the dynamics of a protein will not only give a clearer and a more realistic picture of what the protein looks like in nature -- so that goalie's location and motions are precisely known -- but will also help to develop medicines that can modify the protein's function more accurately and more potently.

Story Source:

The above story is based on materials provided by University of Vienna. Note: Materials may be edited for content and length.

Journal Reference:

  1. Antonija Kuzmanic, Navraj S. Pannu, Bojan Zagrovic. X-ray refinement significantly underestimates the level of microscopic heterogeneity in biomolecular crystals. Nature Communications, 2014; 5 DOI: 10.1038/ncomms4220

Cite This Page:

University of Vienna. "Sometimes the average just isn't good enough: Averaging not always best for analying protein crystal structures." ScienceDaily. ScienceDaily, 10 February 2014. <www.sciencedaily.com/releases/2014/02/140210101941.htm>.
University of Vienna. (2014, February 10). Sometimes the average just isn't good enough: Averaging not always best for analying protein crystal structures. ScienceDaily. Retrieved February 28, 2015 from www.sciencedaily.com/releases/2014/02/140210101941.htm
University of Vienna. "Sometimes the average just isn't good enough: Averaging not always best for analying protein crystal structures." ScienceDaily. www.sciencedaily.com/releases/2014/02/140210101941.htm (accessed February 28, 2015).

Share This

More From ScienceDaily

More Matter & Energy News

Saturday, February 28, 2015

Featured Research

from universities, journals, and other organizations

Featured Videos

from AP, Reuters, AFP, and other news services

Elon Musk's Hyperloop Moves Forward

Elon Musk's Hyperloop Moves Forward

Buzz60 (Feb. 27, 2015) Zipping around at 800-miles an hour is coming closer to reality in California. An entire town is being built around Elon Musk&apos;s Hyperloop concept and it wants you to stop in for a ride when it&apos;s ready. Brett Larson is on board. Video provided by Buzz60
Powered by NewsLook.com
Vibrating Bicycle Senses Traffic

Vibrating Bicycle Senses Traffic

Reuters - Innovations Video Online (Feb. 26, 2015) Dutch scientists have developed a smart bicycle that uses sensors, wireless technology and video to warn riders of traffic dangers. Ben Gruber reports. Video provided by Reuters
Powered by NewsLook.com
In Japan, Robot Dogs Are for Life -- And Death

In Japan, Robot Dogs Are for Life -- And Death

AFP (Feb. 25, 2015) Robot dogs are the perfect pet for some in Japan who go to repairmen-turned-vets when their pooch breaks down - while a full Buddhist funeral ceremony awaits those who don&apos;t make it. Duration: 02:40 Video provided by AFP
Powered by NewsLook.com
London Show Dissects History of Forensic Science

London Show Dissects History of Forensic Science

AFP (Feb. 25, 2015) Forensic science, which has fascinated generations with its unravelling of gruesome crime mysteries, is being put under the microscope in an exhibition of real criminal investigations in London. Duration: 00:53 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.


Breaking News:

Strange & Offbeat Stories

Space & Time

Matter & Energy

Computers & Math

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News


Free Subscriptions

Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile

Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?

Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins