October 27

Awarded Speaker

William F. DeGrado

Department of Pharmaceutical Chemistry, University of California, San Francisco

Michael's photo

Awardee

William (Bill) DeGrado’s work focuses on the design of small molecule drugs, peptides, and proteins to address biological and mechanistic questions. Since 2011, Bill has been a professor in the Department of Pharmaceutical Chemistry at the University of California San Francisco. Prior to UCSF, he was a member of DuPont Central Research and DuPont Merck Pharmaceutical Company from 1981 to 1996, and the Raiziss Professor in the Department of Biochemistry and Biophysics at the University of Pennsylvania (1996 – 2011). He graduated from Kalamazoo College in 1978, received his Ph.D. in organic chemistry from the University of Chicago (1981), and joined DuPont Central Research without an intervening postdoctoral position.

Bill is a member of the United States National Academy of Sciences, American Academy of Arts and Science, the Academy of Inventors, and he has received the top awards from the Protein Society and the Peptide Society. He has also received the Scott award, given by the city of Philadelphia, which is the oldest scientific award in the U.S.

Subject

De Novo Design of Functional Proteins

Lipid De novo protein design involves the creation of proteins from scratch, rather than by modification of natural proteins. A variety of functionally rich proteins have been achieved. Some functions, such as binding to protein interfaces have been relatively easy, because the interactions that stabilize interfaces are also used to stabilize the folded structures of proteins, and available computational methods have been well calibrated to this task. It has been more difficult to design functions that involve molecular recognition of small, polar molecules or dynamic processes. I will describe recent progress in the design of proteins that bind small molecules, and the use of these proteins in potential biomedical applications such as drug targeting, delivery and as drug reversal agents. We also have made progress in the area of the design of proteins with enzymatic activities, including ones that catalyze reactions at rates that exceed most natural enzymes. We also have designed proteins that catalyze reactions for which there were no known protein catalysts.

A second challenging area of interest in de novo protein design has been the construction of useful membrane proteins. I will describe the design of semisynthetic membrane proteins that function as ion channels, and their application to DNA and RNA sequencing. The talk will also demonstrate how de novo design can be used to test the mechanisms by which protons are conducted with high specificity and efficiency through transmembrane proton channels.

Honors and Awards

  • 2021 John Scott Award (City of Philadelphia)
  • 2020 Faraday Metal (Royal Society of Chemistry)
  • 2018 M. Goodman Memorial Prize (ACS), Biological Division)
  • 2018 Cope Scholar Award (American Chemical Society, Organic Division)
  • 2017 Distinguished Alumnus Award (Kalamazoo College)
  • 2016 Max Perutz Memorial Lecture (Weizmann Institute, Israel)
  • 2015 Stein & Moore Award (Protein Society)
  • 2014 National Academy of Inventors
  • 2009 Makineni Award (APS)
  • 2008 Ralph F. Hirschmann Award in Peptide Chemistry (American Chemical Society)
  • 2003 Merrifield Award, Peptide Society
  • 1999 Member, National Academy of Sciences (U.S.A.)
  • 1998 Member, American Academy of Arts and Science
  • 1995 Fellow, American Association for the Advancement of Science
  • 1992 Eli Lilly Award in Biological Chemistry
  • 1989 Protein Society Young Investigator Award
  • 1988 Du Vigneaud Award for Young Investigators in Peptide Research

A nursing room and accessible restroom facilities are available on-site.