December 2009

Retrospective: Charles Tanford (1921–2009)

Charles Tanford was one the great protein chemists of the 20th century. Equally comfortable with experimentation and theory, his contributions were numerous and fundamental, especially those on both protein denaturation and the hydrophobic effect. He was also an exceptional writer. His textbook, “Physical Chemistry of Macromolecules,” was a staple for a generation of biophysics students (including myself), and his reviews in Advances in Protein Chemistry established a paradigm for understanding protein-folding thermodynamics. Upon retirement, he wrote several popular books, each with flair and each reflecting his distinctive view of the subject material. His work conditioned the way we all think about proteins. 

George D. Rose
Krieger-Eisenhower professor of biophysics
Johns Hopkins University

***

Tanford’s contributions on the hydrophobic effect, amino acid solubilities and protein stability are well known. What is less known is that he was also a pioneer in structure-based thermodynamics calculations. In 1957 he published, with John G. Kirkwood, a continuum electrostatics model of proteins. At the time, this was probably the most important paper in the field since Linderstrøm-Lang’s contributions 33 years earlier. The Tanford-Kirkwood model, as it is still known today, was a perfect marriage of Kirkwood’s mathematical skills and Tanford’s deep knowledge of ligand binding and multiple equilibria. With characteristic insight, Tanford, working with Robert Roxby, cast the model as an algorithm that could be solved with an iterative procedure. In 1972, they used it to calculate the proton titration curve of lysozyme starting from the coordinates of the crystal structure. He did not go back to work on this problem, but he sparred and watched closely and with curiosity over the shoulders of younger scientists working in Frank Gurd’s lab to improve Tanford-Kirkwood calculations. Generations of scientists were stimulated by Tanford’s work in protein electrostatics and continue to work on problems that Tanford first brought to the forefront.

Bertrand Garcia-Moreno
Professor and chair of the department of biophysics
Johns Hopkins University

***

Walter Gratzer (walter.gratzer@gmail.com) is a professor of biophysical chemistry at King’s College London.


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