August 8, 2013
“In an advance that will help scientists design and engineer proteins, a team including researchers from SLAC and Stanford has found a way to identify how protein molecules flex into specific atomic arrangements required to catalyze chemical reactions essential for life.
The achievement, published Sunday (Aug. 4, 2013) in Nature Methods, uses a new computer algorithm to analyze data from X-ray studies of crystallized proteins. Scientists were able to identify cascades of atomic adjustments that shift protein molecules into new shapes, or conformations.
This 3-D figure of the enzyme dihydrofolate reductase (dhfr) shows the nine different areas where a small fluctuation in one part of this flexible molecule causes a sequence of atomic movements to propagate like falling dominoes. A new computer algorithm, CONTACT, identified these areas, which are colored red, yellow, green, orange, salmon, grey, light blue, dark blue and purple.
‘Proteins need to move around to do their part in keeping the organism alive,’ said Henry van den Bedem, first author on the paper and a researcher with the Structure Determination Core of the Joint Center for Structural Genomics (JCSG) at the SSRL Directorate of SLAC. ‘But often these movements are very subtle and difficult to discern. Our research is aimed at identifying those fluctuations from X-ray data and linking them to a protein’s biological functions. Our work provides important new insights, which will eventually allow us to re-engineer these molecular machines.'”
Henry van den Bedem. (Matt Beardsley/SLAC)
Central to the new technique is a new computer algorithm, called CONTACT, that analyzes protein structures determined by room temperature X-ray crystallography. Built upon an earlier algorithm created by van den Bedem, CONTACT detects how subtle features in the experimental data produced by changing conformations propagate through the protein and identifies regions within the protein where these cascades of small changes are likely to result in stable conformations.
The research team also included scientists from University of California-San Francisco and The Scripps Research Institute in La Jolla.
See the full article here.
SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the DOE’s Office of Science.
ScienceSprings is powered by MAINGEAR computers