Associate Professor Benjamin Hackel

CSENG Chemical Eng & Mat Sci
College of Science & Engineering
Twin Cities
Project Title: 
Protein Engineering

These researchers engineer high affinity binding proteins, enzymes, and antimicrobial proteins using laboratory directed evolution. Hundreds of millions of protein mutants are produced and tested for functionality (stability and affinity to various targets of interest, catalytic efficiency, and antimicrobial activity) on a weekly basis. Yet this seemingly high throughput does not approach the 10N (N=20-1,000) possible mutants. The group uses computational estimation of protein stability and protein-protein affinity to guide their selection of which mutants to test in the laboratory.

The researchers use several software packages including Rosetta, FoldX, PyMol, and custom codes in Python and Linux. Multiple experimental questions will be asked. How effectively do Rosetta and FoldX predict stabilization resulting from amino acid mutation? Stabilizing mutations will be predicted, and the proteins will be produced and tested for stability in the laboratory. Increased stability has many practical advantages including robustness to industrial use and reduced immunogenicity for clinical use. Moreover, mutants of different stability enable us to assess whether parental protein stability aids evolvability – i.e., does a more stable protein improve the identification of novel functional mutants via directed evolution? Secondly, the researchers use structural and stability analysis to predict which protein topologies will be evolutionarily optimal for the generation of novel binding function.

The group also extensively uses bioinformatics tools for sequence analysis, both of established phylogeny and their own sequence datasets.

Project Investigators

Tsvetelina Baryakova
Paul Blanchard
Adelyn Crabtree
Matt DeJong
Alexander Golinski
Associate Professor Benjamin Hackel
Graduate Student Joseph Hassler
Dr. Andrew Lewis
Patrick Lown
Adam McConnell
Brian Mikolajczyk
Seth Ritter
Vidur Sarma
Zachary Schmitz
Daniel Tresnak
 
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