In this weekly seminar series, Nicholas Polizzi, Assistant Professor for the Department of Biological Chemistry and Molecular Pharmacology at the Dana Farber Cancer Institute, Harvard Medical School, Boston, MA will present a one-hour talk titled:
Designing ligand-binding proteins from scratch
Abstract Most proteins function by first binding a ligand, such as another protein, peptide, or small molecule. The Polizzi laboratory aims to learn the rules of protein–ligand binding through the lens of de novo protein design. In de novo design, a protein’s structure and sequence are computed from first principles. This approach has seen much recent success for the creation of new protein shapes. However, the design of proteins that bind to specific ligands remains an outstanding challenge. In this talk, I will discuss our lab’s approach to designing small-molecule-binding proteins from scratch. By analyzing thousands of protein structures in the Protein Data Bank, we discovered a structural “code” used by proteins to preferentially bind the chemical groups commonly found in small molecules. We developed a design algorithm called COMBS that uses the structural code to create custom ligand-binding sites; and we demonstrated its utility through the design of a de novo protein that specifically binds the antithrombotic drug, apixaban. This work sets the stage for building bespoke ligand-binding proteins with many potential applications in biology and medicine.
This seminar will be presented in the ASRC Auditorium and broadcast via Zoom, with snacks and refreshments to start at 11:30am in the cafe.
To join these ongoing events via Zoom, please use the link below:
Meeting ID: 968 3104 2138
Passcode: ASRC-CDI
For more information about this hybrid event please contact:
Hyacinth Camillieri