Professor William DeGrado

Paul G. Gassman Lectureship in Chemistry
Professor  William DeGrado
Department of Pharmaceutical Chemistry
University of California San Francisco
Host: Professor Mark Distefano

Abstract

Analysis and design of proton transporters

The mechanism of proton transport through membrane proteins is of general interest to multiple areas of biology.  In enveloped RNA viruses, viroporins (viral proton channels) facilitate the transfer of protons through the viral envelope to disrupt protein-RNA interactions required for uncoating, as well as control of the pH of cellular compartments. Using a variety of spectroscopic, crystallographic, and computational methods, we have investigated the mechanism by which protons are conducted through the M2 proton channel from influenza A virus, and used this information to design new anti-influenza drugs that target highly drug-resistant forms of the virus. 

A second topic of the talk will focus on the use of de novo protein design to test the principles underlying membrane protein folding, stability and dynamics.  We have also used this knowledge to design membrane proteins that test the fundamental mechanisms underlying selective transport of protons, and linking proton movement to transport of other ions.

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Research

In the UC San Francisco lab of William DeGrado, PhD, we study the structural characterization of membrane proteins and de novo protein design in order to understand biological processes relevant to human disease and to develop novel therapeutics.

One primary research interest is de novo design, in which one designs proteins beginning from first principles. This approach critically tests our understanding of protein folding and function, while also laying the groundwork for the design of proteins and biomimetic polymers with properties not seen in nature.

De novo design of proteins has proven to be a useful approach for understanding the features in a protein sequence that cause it to fold into its unique three-dimensional structure. It has been possible to design functionally interesting proteins that bind redox-active cofactors, DNA, and transition metals. This approach has been extended to the design of membrane-active proteins, including ion channels, antibiotics, and fusogenic agents.

Professor William DeGrado

De novo protein design; membrane proteins; small molecule drug discovery for antimicrobials, influenza A virus, antifibrotics, and neurodegeneration; chemical biology; peptide design

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Start date
Thursday, Dec. 2, 2021, 9:45 a.m.
End date
Thursday, Dec. 2, 2021, 11 a.m.
Location

This seminar will be presented remotely and live-streamed
331 Smith Hall
Zoom Link