Seminar: "Proteins Under Extreme Conditions"


Prof. Jeremy Palmer, University of Houston, Chem and Biochem. Host: Scott Shell and Luc Jaeger

Date and Location

Wednesday March 01, 2017 11:00am to 12:00pm
Elings 1601


Proteins Under Extreme Conditions

Jeremy C. Palmer

Department of Chemical and Biomolecular Engineering, University of Houston


Bioengineered medicines have emerged as the fastest-growing segment of the pharmaceutical industry over the last several decades. To enhance shelf-life, more than half of these new medicines are formulated as freeze-dried (lyophilized) powders. Freeze-dried biologicals, however, often exhibit reduced therapeutic efficacy when they are reconstituted prior to delivery.  The causes of this activity loss are not fully understood at the molecular level, which poses a considerable challenge to developing strategies for formulating stable therapeutics. My talk will focus on the use of computer simulation techniques to exploring how proteins are affected by exposure to freeze-drying conditions such as extreme states of dehydration and cold temperatures. First, I will describe a computational approach that we recently developed to study water sorption on protein powders, and show that this technique allows us to make rigorous contact with experimental measurements designed to probe the protein dehydration and rehydration processes. The new method also allows us to go beyond the current capabilities of current experimental techniques and investigate how changes in hydration level can give rise to microscopic mechanical stresses that may alter the structure and activity of some proteins.  In the second part of my talk, I will present results from our recent work on using computer simulation to investigate cold unfolding of small globular proteins.  It has long been argued that globular proteins unfold at low temperature due to hydration of residues buried in their hydrophobic core. Although we observe this process in simulation, we show that it is not the dominant thermodynamic factor responsible for cold unfolding.