1350 21 DECEMBER 2018 • VOL 36 2 ISSUE 6421 sciencemag.org SCIENCE
Two research teams simultaneously published papers in October revealing a
new way to determine the molecular structures of small organic compounds
in just minutes, rather than the days, weeks, or months required by tradi-
tional methods.
For decades, the gold standard for molecular mapping has been a technique
known as x-ray crystallography, which involves firing a beam of x-rays at a
crystal containing millions of copies of a molecule lined up in a common orien-
tation. Researchers then track the way x-rays bounce off the crystal to identify
individual atoms and assign them positions in the molecule. The structures are
invaluable for understanding how biological molecules behave and how drugs
interact with them. But the technique requires growing crystals about the size of
a grain of sand, which can be a major hurdle for some substances.
In recent years, researchers have modified the diffraction technique by replac-
ing the x-rays with an electron beam. The electron beam is aimed at a sheetlike
2 D crystal of the target biomolecule, usually a protein. But in some cases, those
sheets stack atop one another, creating a 3 D crystal that doesn’t work for ordi-
nary electron diffraction and is too small for x-ray diffraction.
Two research teams—one in the United States, the other in Germany and
Switzerland—found they could use such accidental crystals after all. They fired
an electron beam at a tiny 3D crystal on a rotating stage and tracked how the
diffraction pattern changed with each slight turn. The technique generated mo-
lecular structures in minutes—from microscopic crystals just one-billionth the
size required for x-ray studies.
Well-suited for mapping small molecules such as hormones and potential
drugs, the new technique should have a profound impact on fields ranging
from the synthesis and discovery of new pharmaceuticals to the design of
molecular probes to study and track diseases. —Robert F. Service
Molecular structures made simple
Structures can now be gleaned from micrometer-size crystals
(black), seen here on an electron microscope slide.An illustration of
detectors buried in
ice beneath the South
Pole that record rare
flashes triggered by
neutrinos.IMAGES:^ (TOPTOBOTTOM) JAMIE^YANG^ ANDSAVANNAHGUTHRIE/ICECUBE/NSF;^ GONENLABPublished by AAASon December 24, 2018^http://science.sciencemag.org/Downloaded from