Nanotechnology Now







Heifer International

Wikipedia Affiliate Button


DHgate

Home > Press > Big data tackles tiny molecular machines:Rice University technique able to analyze conformations of complex molecular machines

Co-evolved mutations in genetic sequences that code proteins show researchers how a protein is likely to fold and what forms it may take as it carries out its function. Scientists at Rice University used the technique called direct coupling analysis in combination with structure-based models to find a previously hidden conformation of a molecular motor responsible for degrading misfolded proteins in bacteria.Credit: Faruck Morcos/Rice University
Co-evolved mutations in genetic sequences that code proteins show researchers how a protein is likely to fold and what forms it may take as it carries out its function. Scientists at Rice University used the technique called direct coupling analysis in combination with structure-based models to find a previously hidden conformation of a molecular motor responsible for degrading misfolded proteins in bacteria.

Credit: Faruck Morcos/Rice University

Abstract:
Open, feed, cut. Such is the humdrum life of a motor molecule, the subject of new research at Rice University, that eats and excretes damaged proteins and turns them into harmless peptides for disposal.

Big data tackles tiny molecular machines:Rice University technique able to analyze conformations of complex molecular machines

Houston, TX | Posted on March 14th, 2014

The why is obvious: Without these trash bins, the Escherichia coli bacteria they serve would die. And thanks to Rice, the how is becoming clearer.

Biophysicists at Rice used the miniscule machine - a protease called an FtsH-AAA hexameric peptidase - as a model to test calculations that combine genetic and structural data. Their goal is to solve one of the most compelling mysteries in biology: how proteins perform the regulatory mechanisms in cells upon which life depends.

The Rice team of biological physicist José Onuchic and postdoctoral researchers Biman Jana and Faruck Morcos published a new paper on the work this month for a special issue of the Royal Society of Chemistry journal, Physical Chemistry Chemical Physics.

The special issue edited by Rice biophysicist Peter Wolynes and Ruth Nussinov, a researcher at the National Cancer Institute in Frederick, Md., and a professor at the Sackler School of Medicine at Tel Aviv University, pulls together current thinking on how an explosion of data combined with ever more powerful computers is bringing about a second revolution in molecular biology.

The paper describes the Onuchic group's first successful attempt to feed data through their computational technique to describe the complex activity of a large molecular machine formed by proteins. Ultimately, understanding these machines will help researchers design drugs to treat diseases like cancer, the focus of Rice's Center for Theoretical Biological Physics.

"Structural techniques like X-ray crystallography and nuclear magnetic resonance have worked quite well to help us understand how smaller proteins function," Onuchic said. X-rays only take snapshots of constantly moving proteins, he said, "but functional proteins, big protein complexes and molecular machines have multiple conformations.

"Computational models are also useful, but to understand the full dynamics of these large proteins, where a lot of the interesting biology takes place, we have to supplement them with more information," he said.

That information comes from direct coupling analysis (DCA), a statistical tool developed by Morcos and Onuchic with colleagues at the University of California, San Diego, and the Pierre and Marie Curie University. DCA looks at the genetic roots of proteins to see how amino acids - the "beads" in the unfolded protein strands — co-evolved to influence the way a protein folds. Each bead carries an intrinsic energy that contributes to the strand's distinct energy landscape, which dictates how it folds into its functional state.

Even after they fold, proteins are in perpetual motion, acting as catalysts for countless bodily functions. They can combine into larger molecular machines that grab other molecules, "walk" cargoes within a cell or cause muscles to contract.

One such biomachine is FtsH, a membrane-bound molecule in E. coli made of six protein copies that form two connected hexagonal rings. The molecule attracts and degrades misfolded proteins and other cellular detritus, pulling them in through one ring, which closes like the shutter of a camera and traps the proteins. They are cut apart as they exit through the other ring.

Through molecular simulations using structure-based models and the discovery via DCA of likely couplings in the genetic source of the proteins, the Rice team found evidence to support the hypothesis of a "paddling" mechanism in the molecule that Morcos described as a collapse of the two rings once trash found its way inside.

"First the ring pore closes to grab the protein; then the molecule flattens," he said. "Then when the motor is flat, the rings open to release the peptides and the molecule expands again to restart the cycle."

Key to the success of DCA is the realization that amino acid mutations represent contacts that co-evolve for specific purposes. The contact maps created by DCA can reveal previously unknown details to model transitions between functional states, like the paddling in FtsH, Onuchic said.

"We can look at the evolutionary tree of these proteins and see which pairs of amino acids changed together. We then assume these are contacts," he said. "Through DCA, Faruck uses a lot of physics to understand when two amino acids can act directly or indirectly, and separate the two. Then we predict how coupled they are, and the higher the probability, the more evidence that these are real contacts."

DCA would do little without the flood of data available since the ability to scan entire genomes became possible, and even commonplace, in recent decades. Advances in the century-old art of crystallography are making better structure-based models available as well.

"Even if the mathematical framework was ready and we had crystallographic data for this motor protein in the 1990s, there weren't enough sequences available until the 2000s," Morcos said. "Now we have all the pieces converging."

He said understanding essential motor proteins in bacteria will be important as researchers begin to apply DCA to advance human health. "For us, the most exciting part is that we're now able to tackle really big systems," Morcos said.

The research was supported by the Center for Theoretical Biological Physics, the Welch Foundation, the National Science Foundation and the Cancer Prevention and Research Institute of Texas. Onuchic is the Harry C. and Olga K. Wiess Chair of Physics and Professor of Physics and Astronomy. Wolynes is the D.R. Bullard-Welch Foundation Professor of Science and a professor of chemistry.

####

About Rice University
Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation’s top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,920 undergraduates and 2,567 graduate students, Rice’s undergraduate student-to-faculty ratio is 6.3-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice has been ranked No. 1 for best quality of life multiple times by the Princeton Review and No. 2 for “best value” among private universities by Kiplinger’s Personal Finance.

Follow Rice News and Media Relations via Twitter @RiceUNews

For more information, please click here

Contacts:
David Ruth
713-348-6327


Mike Williams
713-348-6728

Copyright © Rice University

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related Links

Read the abstract at:

Center for Theoretical Biological Physics:

Related News Press

News and information

Graphene reduces wear of alumina ceramic March 26th, 2015

FEI Technology Award of the German Neuroscience Society Goes to Benjamin Judkewitz of the University of Berlin: Bi-annual award honors excellence in brain research during the German Neuroscience Society’s Annual Meeting, held 18-21 March 2015 March 26th, 2015

SUNY Poly & M+W Make Major Announcement: Major Expansion To Include M+W Owned Gehrlicher Solar America Corporation That Will Create up to 400 Jobs to Develop Solar Power Plants at SUNY Poly Sites Across New York State March 26th, 2015

Hong Kong Investors Bullish on Dais Analytic Invest $5.75M, Provide $60M Contract, and Create New Joint Venture Company March 26th, 2015

Govt.-Legislation/Regulation/Funding/Policy

SUNY Poly & M+W Make Major Announcement: Major Expansion To Include M+W Owned Gehrlicher Solar America Corporation That Will Create up to 400 Jobs to Develop Solar Power Plants at SUNY Poly Sites Across New York State March 26th, 2015

Thousands of atoms entangled with a single photon: Result could make atomic clocks more accurate March 26th, 2015

ORNL-led team demonstrates desalination with nanoporous graphene membrane March 25th, 2015

Carbon nanotube fibers make superior links to brain: Rice University invention provides two-way communication with neurons March 25th, 2015

Molecular Machines

Tiny bio-robot is a germ suited-up with graphene quantum dots March 24th, 2015

New remote control for molecular motors: It is now theoretically possible to remotely control the direction in which magnetic molecules spin, which opens the door to designing applications based on molecular motors March 16th, 2015

Monitoring the real-time deformation of carbon nanocoils under axial loading February 18th, 2015

Stomach acid-powered micromotors get their first test in a living animal January 27th, 2015

Discoveries

Graphene reduces wear of alumina ceramic March 26th, 2015

Quantum compute this -- WSU mathematicians build code to take on toughest of cyber attacks: Revamped knapsack code offers online security for the future March 26th, 2015

Thousands of atoms entangled with a single photon: Result could make atomic clocks more accurate March 26th, 2015

Square ice filling for a graphene sandwich March 26th, 2015

Announcements

Industrial Nanotech, Inc. Announces Next Large Order from the Oil and Gas Industry March 26th, 2015

Quantum compute this -- WSU mathematicians build code to take on toughest of cyber attacks: Revamped knapsack code offers online security for the future March 26th, 2015

Thousands of atoms entangled with a single photon: Result could make atomic clocks more accurate March 26th, 2015

Square ice filling for a graphene sandwich March 26th, 2015

Interviews/Book Reviews/Essays/Reports/Podcasts/Journals/White papers

Graphene reduces wear of alumina ceramic March 26th, 2015

Quantum compute this -- WSU mathematicians build code to take on toughest of cyber attacks: Revamped knapsack code offers online security for the future March 26th, 2015

Thousands of atoms entangled with a single photon: Result could make atomic clocks more accurate March 26th, 2015

Square ice filling for a graphene sandwich March 26th, 2015

Grants/Awards/Scholarships/Gifts/Contests/Honors/Records

FEI Technology Award of the German Neuroscience Society Goes to Benjamin Judkewitz of the University of Berlin: Bi-annual award honors excellence in brain research during the German Neuroscience Society’s Annual Meeting, held 18-21 March 2015 March 26th, 2015

FEI Announces Image Contest Grand Prize Winner: Francisco Rangel of the National Institute of Technology, INT/MCTI, Brazil, wins the contest with his “Expanded Vermiculite” image March 23rd, 2015

Halas, Nordlander awarded Optical Society's R.W. Wood Prize: Rice University researchers recognized for pioneering nanophotonics March 21st, 2015

Hiden Instruments identified in London Stock Exchange’s ‘1000 Companies to Inspire Britain' March 21st, 2015

NanoNews-Digest
The latest news from around the world, FREE




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More










ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project







© Copyright 1999-2015 7th Wave, Inc. All Rights Reserved PRIVACY POLICY :: CONTACT US :: STATS :: SITE MAP :: ADVERTISE