The death of Loeb Professor of Biophysics and Biochemistry Don C. Wiley marks both a personal loss for his family and friends and a loss for the entire field of structural biology, his colleagues say.

“Don is not replaceable,” said Higgins Professor of Biochemistry Jack L. Strominger, who worked closely with Wiley for about 15 years in the 1980s and early 1990s, helping him on some of his key discoveries. “He had so much experience and knowledge in the field and was so outstanding.”

Wiley was a prolific scientist, publishing scores of papers that explained the structures of molecules in human cells.

His work, which used the structure of molecules to help understand their function, has become common textbook fare. Studying proteins in the immune system and on certain viruses, Wiley helped explain the way the body defends itself against disease.

“Don always had a way of figuring out the essence of a question,” said Higgins Professor of Biochemistry Stephen C. Harrison who published several papers with Wiley in the last few years. “It’s the clarity of the description of his discoveries that we will especially miss.”

“That he will no longer be doing research is a great loss to the field,” said Higgins Professor of Biochemistry Guido Guidotti.

Especially important were Wiley’s determinations of the structures of key molecules in the human immune system. Starting in the early 1980s and working with Strominger, Wiley solved the structure of many molecules central to immunity.

One of those proteins, called a class I major histocompatibility complex (MHC) molecule, helps the body identify cells that have been infected with viruses. The molecule, which comes in several different variations, is able to bind to pieces of thousands of different types of viruses. The way the molecule binds and presents the pieces to the immune system was a mystery until Wiley’s work on the subject in the 1980s.

In 1987, Wiley and then-postdoctoral fellow Pamela J. Bjorkman used a technique called x-ray crystallography to determine the three-dimensional positions of all the atoms in the class I MHC molecule.

According to Harrison, the application of x-ray crystallography to proteins on the surface of the cell was one of Wiley’s great accomplishments.

“All the structure work was done in his lab,” Strominger said. “No one knows if someone else could have accomplished it. It was so difficult.”

When Wiley started his work, it was not even clear if such cell-surface proteins had definite shapes that could be determined with x-ray crystallography.

Wiley proved that such experiments could be done, and consistently used the technique to solve new problems.

Working in collaboration with Strominger, Wiley also determined the structures of other molecules in the immune system and of many different viral proteins.

Harrison said that Wiley had a knack for interpreting complex structures.