McGee Lecture Series

The Henry A. McGee Lectures in Chemical and Life Science Engineering honor the founding dean of VCU’s School of Engineering, Henry A. McGee, who is also a distinguished Emeritus professor in the Chemical and Life Science Engineering department. The lecture series is made possible by the Betty Rose and Henry McGee Endowment for Chemical Engineering. Learn more about Dr. Henry McGee.

Event Details

Date: Thursday, April 20, 2023
Time: 2–3 p.m.
Location: Engineering Research Building, Room 1313

Lecture title

Computational Design of Peptides as Detectors, Sensors and Drugs

Bio

Professor Carol K. Hall is the Worley H Clark, Jr. Distinguished University Professor of Chemical and Biomolecular Engineering at North Carolina State University. She received her B.A. in physics from Cornell University and her Ph.D. in physics from the State University of New York at Stony Brook. After postdoctoral training in the Chemistry Department at Cornell and a brief period as an economic modeler at Bell Laboratories, she joined the Chemical Engineering Department at Princeton University in 1977 as one of the first women to be appointed to a chemical engineering faculty in the U.S. In 1985 she joined the Chemical Engineering Department at North Carolina State University. Hall’s research focuses on applying statistical thermodynamics and molecular-level computer simulation to topics of chemical, biological or engineering interest involving macromolecules, soft matter and complex fluids. Current research topics include protein folding/aggregation, multipolar colloids, protein or peptide design, and remediation of microplastic pollution. The author of over 300 publications, she is a recipient of the AIChE 2015 Founders Award and the 2019 John M Prausnitz Award from the PPEPPD Thermodynamics Conferences. She is a Fellow of the American Institute of Chemical Engineers, the American Physical Society and the American Association for the Advancement of Science. In 2020 she was awarded the AIChE Margaret Hutchinson Rousseau Pioneer Award for Lifetime Achievement by a Woman Chemical Engineer. Hall was elected to the National Academy of Engineering in 2005 and now serves as its Home Secretary.

Abstract

We describe our efforts to develop an efficient computational algorithm that searches for peptides that bind strongly and selectively to specific biomolecular targets, and to use that algorithm in the design of peptide-based sensors, drugs and affinity chromatography ligands. The algorithm is an iterative procedure that involves as many as 50,000 sequence mutation moves and/or peptide backbone conformation moves to arrive at the peptide sequence and conformation that has the lowest binding energy to the target. The top scoring peptides are then further evaluated by performing explicit-solvent atomistic simulations of the peptide–target complex to determine their binding free energies. The biomarker chosen for initial study was Cardiac Troponin I, a 210-amino acid protein that is elevated in the blood of heart attack victims. The top-scoring peptides were synthesized by collaborators at the Air Force Research Laboratory who then used a variety of experimental techniques to assess the binding capabilities of the top candidate peptides. The measured binding affinity of the designed variant, P2, for cTnI was extremely strong (KD = 0.27 nM) and comparable to that of the natural antibody (KD = 0.12 nM). We further describe two other projects: (1) design of peptide affinity ligands for bioseparating monoclonal antibody, IgG, from the cell cultures in which they are synthesized, and (2) design of peptides to block the action of the toxins secreted by C- difficile bacteria in the large intestine.

Past Speakers

• 2022–Piero Baglioni, Ph.D.
• 2021–Dong-Pyo Kim, Ph.D.
• 2020–Monty Alger, Ph.D.
• 2019–Klavs Jensen, Ph.D.
• 2018–Babatunde Ogunnaike, Ph.D.
• 2017–Robert Prud'homme, Ph.D.
• 2016–Gregory Stephanopoulos, Ph.D.
• 2015–Vicki L. Colvin, Ph.D.
• 2014–Benny D. Freeman, Ph.D.
• 2013–Mark E. Davis, Ph.D.
• 2012–Jay Keasling, Ph.D.
• 2011–Joseph M. DeSimone, Ph.D.
• 2010–Charles Liotta, Ph.D.