Alex Hoffnagle

I am a computational protein design scientist at Profluent Bio with experience in computational protein design and experimental protein characterization. My interests lie in using advanced computational tools to push the boundaries of computational protein design. I received my Bachelor's and Master's degrees from the University of Pennsylvania, where I was a Roy and Diana Vagelos Molecular Life Sciences scholar. At UPenn, I received a strong education in chemistry and physics, and I performed undergraduate research in the lab of Dr. Jessica Anna, where I used linear and two-dimensional infrared spectroscopy to study the effects of hydrogen bonding on the vibrational modes of phylloquinone, the terminal electron acceptor of photosystem I. I then moved to UC San Diego for my Ph.D., where I developed computational approaches for the de novo design of metalloenzymes. Using Rosetta and machine learning approaches such as RFDiffusion and MPNN, I accurately designed protein assemblies with new-to-nature metal centers and functions. I also experimentally characterized these designed proteins with X-ray crystallography, enzyme assays, and various spectroscopic techniques to demonstrate the accuracy of the design approaches and explore the fundamental requirements for enzymatic activity in de novo designed metalloproteins.