Navigation Links
Scientists reduce protein crystal damage, improve pharmaceutical development
Date:12/18/2013

New recommendations for using X-rays promise to speed investigations aimed at understanding the structure and function of biologically important proteins information critical to the development of new drugs. Scientists from two U.S. Department of Energy national laboratories, Argonne and Brookhaven, and the University of Washington, Seattle, evaluated options to remedy problems affecting data collection in their new study.

Scientists who use powerful X-ray beams to study protein crystals face a dilemma: the beams provide the best tool for understanding a protein's structure and biological function, but they often damage the crystal, which may require repeated experiments that add time and cost to the research.

"Although X-ray crystallography is the go-to technique for determining protein structure and function, it is not without problems," said Andrzej Joachimiak at Argonne. The use of powerful X-ray beams causes radiation damage resulting in loss of data and the weak diffraction of crystals. In the end, this leads to an incomplete picture of the structure, and of how molecules interact with each other and their environment.

"The problem occurs when a protein crystal absorbs energy from incoming X-rays, which emits electrons that destroy or alter parts of the sample," Joachimiak said.

The research team examined three different X-ray-based methods for solving protein structures and recommended one called "submicrometer line focusing" as the most promising for easing the dilemma. As its name suggests, the beam strikes the protein crystal with an area smaller than a micrometer, or smaller than one thousandth of a millimeter. The tiny impact area minimizes damage. Also like its name, the beam is focused as a vertical line, delivering a more concentrated dose of X-rays per area.

The researchers also suggested using a new lens they designed that breaks the powerful beam into many mini-beams, spaced far enough apart that the damage one mini-beam creates lies outside the area probed by neighboring mini-beams.

"By carefully spacing the beams, we can lessen the damage, gather better data, and do it faster," said Joachimiak. "And because there are several beams rather than just one being released simultaneously, we can collect a greater quantity of useful data."

Synchrotron facilities like the DOE's Advanced Photon Source (APS) at Argonne contain particle accelerator systems designed to produce extraordinarily bright and high-energy X-ray beams. At these facilities, scientists can peer deeply into the atomic structure of molecules using the method of X-ray crystallography.

Scientists need to see what molecules, particularly proteins, look like. While molecules are too small to be visualized directly, their shape can be reconstructed by looking at the patterns of how X-rays diffract, or scatter, off them. Crystallography uses crystals of proteins because crystals have repeating patterns that give scientists enough data to reconstruct the exact shape as a 3-D model. From this form, scientists can often determine chemical interactions and processes that can be used to design pharmaceuticals.

In this study, the team looked at the penetration depth of the damaging electrons and at the spread or distribution of the damaged area on the protein crystal. While earlier studies recognized the issue, this team is the first to collect high-resolution data and directly measure the damaged area using a line focus beam. The team also found that earlier work had underestimated the depth of the problem.

The findings will aid synchrotron researchers as they continue to develop more brilliant and powerful instruments such as those at the APS.


'/>"/>

Contact: Jared Sagoff
jsagoff@anl.gov
630-252-5549
DOE/Argonne National Laboratory
Source:Eurekalert  

Related medicine news :

1. Scientists solving the mystery of human consciousness
2. Scientists uncover multiple faces of deadly breast cancer
3. Scientists identify major source of cells defense against oxidative stress
4. Scientists tailor cell surface targeting system to hit organelle ZIP codes
5. Scientists rewrite rulebook on breast cancer in landmark global study
6. Warwick scientists uncover how checkpoint proteins bind chromosomes
7. NIH scientists link quickly spreading gene to Asian MRSA epidemic
8. Joslin scientists identify important mechanism that affects the aging process
9. Scripps Research scientists show how memory B cells stay in class to fight different infections
10. Scientists Map Melanomas Genome
11. A*STAR scientists discover switch to boost anti-viral response to fight infectious diseases
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Scientists reduce protein crystal damage, improve pharmaceutical development
(Date:2/12/2016)... , ... February 12, 2016 ... ... today announced a new initiative—the Siemens Foundation-PATH Ingenuity Fellowships—to develop the advanced ... will recruit top students from U.S. universities who will draw from Siemens’ ...
(Date:2/12/2016)... ... ... Each year, the American Physical Therapy Association (APTA) offers a Combined Sections Meeting. ... Almost 10,000 physical therapists across the country are expected to attend this annual convention ... field and network with their colleagues. As in years past, HydroWorx is proud ...
(Date:2/12/2016)... ... February 12, 2016 , ... The ThedaCare ... San Francisco General Hospital on April 5-7. The series is a multi-day, multi-workshop ... habits. The workshops cover a broad range of topics, including coaching skills, the ...
(Date:2/12/2016)... NC (PRWEB) , ... February 12, 2016 , ... AssureVest ... surrounding areas, is initiating a charity drive that will raise funds earmarked to purchase ... John C. Tayloe Elementary School. , “My school is in a low-income area and ...
(Date:2/12/2016)... ... February 12, 2016 , ... Young Asset ... celebrates the beginning of the latest charity campaign in their community enrichment program. ... Donations to this worthy cause are currently being accepted at: http://artexpressioninc.org/ . ...
Breaking Medicine News(10 mins):
(Date:2/12/2016)... LOUISVILLE, Ky. , Feb. 12, 2016 ... it has completed a $47.1 million Series ... investors Cormorant Asset Management, Hillhouse Capital Group ... investors Morningside Venture Investments, AJU IB Investment, ... will be used to further advance clinical ...
(Date:2/11/2016)... , Feb. 11, 2016 Stem cells are ... characterized by self-renewal and the capacity to differentiate into ... new discovery, as the first mouse embryonic stem cells ... not until 1995 that the first culturing of embryonic ... cells were not produced until 2006 As a result ...
(Date:2/11/2016)... , Feb. 11, 2016  Governor Andrew M. Cuomo ... create 1,400 jobs throughout Western New York ... with the SUNY Polytechnic Institute, includes a major expansion ... in Buffalo , as well as ... facility in Dunkirk . The combined ...
Breaking Medicine Technology: