Navigation Links
Bringing out the best in X-ray crystallography data

"Function follows form" might have been written to describe proteins, as the M. C. Escher-esque folds and twists of nature's workhorse biomolecules enables each to carry out its specific responsibilities. Technology's workhorse for determining protein structures is X-ray protein crystallography, in which a beam of x-rays sent through a crystallized protein is scattered by the protein's atoms, creating a diffraction pattern of dots that can be reconstructed by computer into a 3D model.

While synchrotron radiation facilities, such as Berkeley Lab's Advanced Light Source, have been a boon to the field of protein crystallography, providing increasingly higher resolution structures over increasingly shorter time-spans, the technology is still a challenge. For some molecules, especially large molecular complexes, it is often only possible to obtain low-resolution experimental data, which means models are difficult to make and must be manually refined using computer modeling.

"Refinement of protein and other biomolecular structural models against low-resolution crystallographic data has been limited by the ability of current methods to converge on a structure with realistic geometry," says Paul Adams, a bioengineer with Berkeley Lab's Physical Biosciences Division and leading authority on x-ray crystallography, who, starting in 2000, has been leading the development of a highly successful software program called PHENIX (Python-based Hierarchical ENvironment for Integrated Xtallography) that automates crystallography data analysis.

Now, Adams and a team that included Nathaniel Echols in his research group, and Frank DiMaio with the research group of David Baker at the University of Washington, have developed a new method for refining crystallographic data that combines aspects of PHENIX with aspects of Rosetta, the most widely used software for the prediction and design of the three-dimensional structure of proteins and other large biomolecules.

The Rosetta program, which was originally developed by Baker and his research group, utilizes a detailed all-atom force field plus a diverse set of search procedures for the creation of its 3D models. PHENIX assembles 3D models atom-by-atom through the extraction of the best data from X-ray measurements. One of the most important components of PHENIX is "phenix.refine," a program for improving these models against the X-ray data using maximum likelihood methods. It was this feature that was combined with Rosetta.

"Our new method integrates the Rosetta and PHENIX programs directly in a flexible framework that allows it to be adapted to a wide variety of different scenarios," says Echols. "The main advantage of our method is that it can aggressively optimize models to fit the data and also present realistic geometry. In general, it has been difficult to come up with methods that handle both of these demands. As a result, crystallographers have either spent a lot of time fixing errors, or the published structures end up being of poor quality."

Echols is one of two lead authors, along with DiMaio, of a paper in Nature Methods describing this work. The paper is titled "Improved low-resolution crystallographic refinement with Phenix and Rosetta." In addition to Adams and Baker, other co-authors are Jeffrey Headd and Thomas Terwilliger. Adams and Baker are the corresponding authors.


Contact: Lynn Yarris
DOE/Lawrence Berkeley National Laboratory

Related biology news :

1. Bringing down the cost of fuel cells
2. Bringing natural history collections out of the dark
3. Roots and microbes: Bringing a complex underground ecology into the lab
4. Bringing measuring accuracy to radical treatment
5. Bringing big data to biodiversity
6. Neuroscience symposium bringing top scientists to Louisville, Aug. 1-2
7. Pitt treats gum disease by bringing needed immune cells to inflamed tissue
8. Dental X-rays linked to common brain tumor
9. Stanford-SLAC team uses X-ray imaging to observe running batteries in action
10. Speed and power of X-ray laser helps unlock molecular mysteries
11. Low-cost carbon capture gets X-rayed
Post Your Comments:
Related Image:
Bringing out the best in X-ray crystallography data
(Date:10/6/2015)... 2015 Track Group, Inc. (OTCQX: TRCK), a ... signed a contract with the Virginia Department of Corrections ... of sentences under the Department,s oversight. Derek ... contract with the Virginia DOC will expand our footprint ... our position as a trusted leader in offender electronic ...
(Date:10/2/2015)... 02 2015 ... "Enforcing the Law Using Biometrics" report to ... announced the addition of the "Enforcing the ... --> Research and Markets ( ... "Enforcing the Law Using Biometrics" report to ...
(Date:9/30/2015)... 2015  The U.S. Court of Appeals for the ... in favor of Crossmatch ™, affirming the International ... Suprema and its U.S. partner Mentalix violated Section 337 ... that declares it unlawful to engage in "unfair practices" ... Crossmatch,s patents, the 5,900,993 patent and the 7,203,344 patent. ...
Breaking Biology News(10 mins):
(Date:10/13/2015)... ... October 13, 2015 , ... The ... school age children in the areas of Science, Technology, Engineering and Mathematics. The ... national economy, and the program aims to increase the number of students who ...
(Date:10/12/2015)... South Carolina (PRWEB) , ... October 12, 2015 , ... ... to announce the release of the CSM-C 600 compact clean steam generator . ... saturated steam that meets the requirements of HTM2031, HTM2010, and EN285 standards. The ...
(Date:10/12/2015)... , Oct. 12, 2015  Rebiotix Inc. today ... has designated its lead Microbiota Restoration Therapy (MRT) ... of recurrent Clostridium difficile (C diff) ... that causes 29,000 deaths in the U.S. annually. ... company that was founded to revolutionize the treatment ...
(Date:10/12/2015)... , Oct. 12, 2015 /PRNewswire/ - Aeterna Zentaris ... biopharmaceutical company engaged in developing and commercializing novel treatments ... departure of Dennis Turpin , the Company,s former ... to close its Quebec City ... President and Chief Executive Officer of the Company commented, ...
Breaking Biology Technology: