Using cutting-edge technologies, scientists today can piece together or even directly view the atomic structures of very large molecules such as proteins that are invisible to the naked eye.
One of the most powerful tools for achieving this is X-ray crystallography, which involves directing an X-ray beam at a crystallized form of a molecule. Upon hitting the crystal, the X-rays are scattered, producing a distinctive pattern. Scientists can then analyze the patterns of the scattered X-rays to determine the positions and identities of the atoms in a molecule (i.e., the three-dimensional molecular structure).
Caltech has been at the forefront of developing X-ray crystallography to determine molecular structures since the time the Institute’s first PhD was awarded to physical chemist Roscoe Dickinson in 1920. Dickinson subsequently joined the faculty and trained Linus Pauling (PhD ’25), who went on to become the only person to receive two unshared Nobel Prizes. During three decades on the Institute faculty, Pauling established a world-renowned center for X-ray crystallography at Caltech and trained generations of students and postdoctoral fellows in the craft. The molecular structures determined in that era were instrumental in Pauling’s transformative formulations of the nature of the chemical bond and the fundamentals of protein structure.
While the technique was limited to small molecules composed of only a few atoms when it debuted a century ago, today X-ray crystallography can be applied to much larger molecular assemblages and proteins.
Don Voet wonders what might have been possible if, as a graduate student, he had had access to instruments as powerful as those that exist today. After graduating from Caltech, he earned his PhD from Harvard University, where his adviser was William Lipscomb (PhD ’46), a former student of Pauling.
“My PhD involved solving the structure of two small molecules,” Don Voet says. “It took years of work because the data collection was very slow, and computational methods were relatively primitive. Now, it can be done in an afternoon, and almost completely hands off.”
The recent advances in X-ray crystallography have been enabled largely by upgrades in instrumentation, including the use of synchrotrons to generate finely tuned X-ray beams of specific wavelengths. For years now, the Caltech community has benefited from significant access to beam line 12-2 (BL12-2), a powerful X-ray source at the Stanford Synchrotron Radiation Laboratory (SSRL). BL12-2 has proven valuable for research as well as for education. For example, students in the graduate course BMB/Ch 230 use the instrument to determine the structure of macromolecules.
BL12-2 is operated by the Molecular Observatory, which Caltech created in 2003 with initial support from the Gordon and Betty Moore Foundation. The goal was to provide the Institute community with exceptional capabilities in macromolecular crystallography.
“The Molecular Observatory has allowed groups that traditionally have not integrated X-ray crystallography into their research a relatively easy way to do so,” says Doug Rees, faculty adviser for the Molecular Observatory. Rees, Caltech’s Roscoe Gilkey Dickinson Professor of Chemistry and a Howard Hughes Medical Institute investigator, also completed his doctoral studies with Lipscomb.
The initial funding for the Molecular Observatory enabled Caltech to operate BL12-2 for 12 years, but that support ended last August. Fortunately, thanks to the Voets’ generous $137,500 gift, Caltech researchers have had access to the beam line for an additional academic year.
“The Voets’ contribution has been essential in maintaining access to beam line 12-2 at SSRL that is central to Caltech’s structural biology research efforts,” Rees says. “It’s really enabled this research to continue taking advantage of and building upon the great resources that the Gordon and Betty Moore Foundation provided.”
Don Voet is an emeritus professor of chemistry at the University of Pennsylvania. Judith Voet is the James Hammons Professor, Emerita, in the Department of Chemistry and Biochemistry at Swarthmore College. The Voets have published biochemistry textbooks that are widely used in undergraduate and graduate courses and are past editors-in-chief of the journal Biochemical and Molecular Biology Education.
As an undergraduate chemistry major at Caltech, Don Voet took a freshman chemistry course taught by Pauling himself. “He was a fantastic teacher,” Don recalls.
He remembers his time at Caltech with fondness and gratitude. He worked in a chemistry lab, played water polo, and made lots of friends. “I kind of grew up there,” he says.
As chemists themselves, the Voets understand the powerful effect that beam line access can have on research at an institution. “At Swarthmore College where I taught, there are now people able to do crystallography because they can get access to a beam line and the expertise necessary to solve crystal structures,” Judith says.
So, when the couple decided they wanted to make a donation associated with chemistry, they naturally thought of Caltech. “I have no connection with Caltech,” Judith says, “but I married the man, and Don believes that Caltech was where he was formed as a scientist. We want to give back so that other people can have that same experience.”