Featured Research

from universities, journals, and other organizations

New Computer Simulation Helps Explain Folding In Important Cellular Protein

Date:
August 11, 2009
Source:
University of Georgia
Summary:
Scientists have created a two-step computer simulation (using an important process called the Wang-Landau algorithm) that sheds light on how a crucial protein -- glycophorin A -- becomes an active part of living cells. The new use of Wang-Landau could lead to a better understanding of the controlling mechanisms behind protein folding.

Most parts of living organisms come packaged with ribbons. The ribbons are proteins—chains of amino acids that must fold into three-dimensional structures to work properly. But when for any reason the ribbons fold incorrectly, bad things can happen, and in humans misfolded-protein disorders include Alzheimer’s and Parkinson’s diseases.

Scientists have for the past three decades tried to understand what makes proteins fold into functional units and why it happens, and several breakthroughs have occurred through computer modeling—a field that dramatically increases analytical speed.

Now, scientists at the University of Georgia have created a two-step computer simulation (using an important process called the Wang-Landau algorithm) that sheds light on how a crucial protein—glycophorin A—becomes an active part of living cells. The new use of Wang-Landau could lead to a better understanding of the controlling mechanisms behind protein folding.

“Our goal is to present the methodology in a clear, self-consistent way, accessible to any scientist with knowledge of Monte Carlo simulations,” said David Landau, distinguished research professor of physics at the University of Georgia and director of the Center for Simulational Physics.

The research was just published in The Journal of Chemical Physics. Authors of the paper are Clare Gervais and Thomas Wόst, formerly of UGA and now employed in Switzerland; Landau, and Ying Xu, Regents-Georgia Research Alliance Eminent Scholar and professor of bioinformatics and computational biology, also at UGA.  Landau and Xu are in UGA’s Franklin College of Arts and Sciences.

“This work demonstrates the power and potential of combining expertise from computational physics and computational biology in solving challenging biological problems,” said Xu.

Monte Carlo simulations—the use of algorithms with repeated random samplings to produce reliable predictions—have been around for some decades but have been steadily refined. These simulations are useful for extremely complex problems with multiple variables, and though they often require considerable computer “brain power,” they are able to give scientists startlingly accurate predictions of how biological processes work.

In the current paper, the research team developed a two-step Monte Carlo procedure to investigate, for glycophorin A (GpA), an important biochemical process called dimerization. (A dimer in biology or chemistry consists of two structurally similar units that are held together by intra- or intermolecular forces.)

“One particularly promising approach is to investigate the thermodynamics of protein folding through examining the energy landscape,” Landau explained. “By doing this, we can learn about the characteristics of proteins including possible folding pathways and folding intermediates. Thus, it allows us to bridge the gap between statistical and experimental results.”

Unfortunately, so much is happening physically and biochemically as proteins fold into their functional shapes (called the native state) that the problems must be broken down one by one and studied. That led the team to a question: Could they use a Monte Carlo Simulation along with the Wang-Landau algorithm to discover an efficient simulation method capable of sampling the energy density states that allow such folding?

Perhaps remarkably, they did. The first step in studying the dimerization process was to estimate those states in GpA using Wang-Landau. The second step was to sample various energy and structural “observables” of the system to provide insights into the thermodynamics of the entire system.

The results could be broadly applied to many fields of protein-folding studies that are important to understanding—and treating—certain diseases. (Wang-Landau, named for David Landau and Fugao Wang, is a Monte Carlo algorithm that has proved to be useful in studying a variety of physical systems. Wang was a doctoral student at UGA and now works for the Intel Corp.)

GpA is a 131-amino acid protein that spans the human red-blood cell membrane and is crucial in cell procedures. Because it has been studied in depth for many years, it also serves as an important model system for how similar systems work. That’s why the new simulation may open doors in many other areas of inquiry.

“The main advantage of this two-step approach lies in its flexibility as well as its generality,” said Landau. “This method is widely applicable to any study of biological systems, such as the folding process of soluble proteins, polymers, DNA or protein complexes. Therefore, it is an excellent alternative to other simulation methods used traditionally in the field of protein-folding thermodynamics.”

In the current study, the team discovered something generally important about membrane proteins in general, too. They found that unlike some proteins for which folding is mainly governed by their attraction to or repulsion by water, the process in GpA is driven by a subtle interplay between multiple types of interactions.

The research was supported by grants from the National Institutes of Health and the National Science Foundation.


Story Source:

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


Cite This Page:

University of Georgia. "New Computer Simulation Helps Explain Folding In Important Cellular Protein." ScienceDaily. ScienceDaily, 11 August 2009. <www.sciencedaily.com/releases/2009/07/090729121706.htm>.
University of Georgia. (2009, August 11). New Computer Simulation Helps Explain Folding In Important Cellular Protein. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2009/07/090729121706.htm
University of Georgia. "New Computer Simulation Helps Explain Folding In Important Cellular Protein." ScienceDaily. www.sciencedaily.com/releases/2009/07/090729121706.htm (accessed August 28, 2014).

Share This




More Plants & Animals News

Thursday, August 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Killer Amoeba Found in Louisiana Water System

Killer Amoeba Found in Louisiana Water System

AP (Aug. 28, 2014) — State health officials say testing has confirmed the presence of a killer amoeba in a water system serving three St. John the Baptist Parish towns. (Aug. 28) Video provided by AP
Powered by NewsLook.com
Raw: Australian Sheep Gets Long Overdue Haircut

Raw: Australian Sheep Gets Long Overdue Haircut

AP (Aug. 28, 2014) — Hoping to break the record for world's wooliest, Shaun the sheep came up 10 pounds shy with his fleece weighing over 50 pounds after being shorn for the first time in years. (Aug. 28) Video provided by AP
Powered by NewsLook.com
Minds Blown: Scientists Develop Fish That Walk On Land

Minds Blown: Scientists Develop Fish That Walk On Land

Newsy (Aug. 28, 2014) — Canadian scientists looking into the very first land animals took a fish out of water and forced it to walk. Video provided by Newsy
Powered by NewsLook.com
Fake Dogs Scare Real Geese from Wis. Park

Fake Dogs Scare Real Geese from Wis. Park

AP (Aug. 28, 2014) — Parks officials in Stevens Point, Wisconsin had a fowl problem. Canadian Geese were making a mess of a park, so officials enlisted cardboard versions of man's best friend. (Aug. 28) Video provided by AP
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.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

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