Thinking inside the box

  • Jun 26, 2016
  • Faculty & Staff, Research, Chemistry

Michael Liebman

Michael Liebman poses with the threee-dimensional wire structure of the enzyme alpha-chymotrypsin -- a pancreatic proteolytic enzyme of the serine protease family -- that he helped design and build as a student under the direction of MSU's Alexander Tulinsky.

Like most of his colleagues in the early 1970s, Michael Liebman (Ph.D., ’75, physical chemistry) was thinking inside the box. That’s when he and several other MSU graduate students used what is called the Richards Box to build a three-dimensional wire structure of the enzyme alpha-chymotrypsin—a pancreatic proteolytic enzyme of the serine protease family.

The model was built under the direction of MSU’s Alexander Tulinsky, University Distinguished Professor Emeritus, as a way to understand how the molecule actually worked, in order to solve the structure and then use that information to solve chemical problems.

“Serine proteases represent a major class of physiologically important enzymes—for example, for blood coagulation—and understanding the relationship between their structure and function can have great potential clinical value in diagnostics and drug development,” said Liebman, co-founder and managing director of IPQ Analytics, LLC, an emerging life sciences and healthcare analytics business in Kennett Square, Penn.

The model itself, 40 x 50 x 50 inches, was built using engineered components and two additional elements. All of the parts together made up the Richards Box.

“We designed and constructed everything ourselves; only the molecular parts were pre-made, and they cost $2,500 in those days!  Now everything is done on a computer,” said Liebman, who is also adjunct professor of pharmacology and physiology at Drexel College of Medicine in Philadelphia, and adjunct professor of medicine at First Hospital of Wenzhou Medical University in Wenzhou, China.

Tulinsky’s model now resides in the Chemical Heritage Foundation Museum in Philadelphia. This nonprofit foundation traces the history of chemistry from alchemy to modern times, and having this model on display highlights its importance as one of the first protein structures solved by crystallography—whereas today, more than 25,000 are known and publicly accessible in the Protein Data Bank. 

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