As a student in the Donald Lab, my research focuses on using structure-based computational protein design to design inhibitors for protein-protein interactions. I work on a variety of projects including re-designing HIV antibodies, designing peptides to target difficult-to-treat cancers such as pancreatic ductal adenocarcinoma, re-designing protein-protein interfaces, and computationally evaluating the stability of proteins. I also work on developing and validating the accuracy of algorithms for OSPREY, a software package developed and maintained by the Donald Lab.


Two first author manuscripts currently in progress:

1. Novel, Provable Algorithms for Efficient Ensemble-Based Protein Design and Their Application to the Redesign of the c-Raf-RBD:KRas Protein-Protein Interface

2. A Thiol Exchange Assay for High-Throughput Screening of Protein Stability with Computationally Designed, Stability-Neutral Cysteine Variants

Jou, J.D.*, Holt, G.T.*, Lowegard, A. U., & Donald, B.R. (2019). Minimization-Aware Recursive K* (MARK*): A Novel, Provable Algorithm that Accelerates Ensemble-based Protein Design and Provably Approximates the Energy Landscape. In International Conference on Research in Computational Molecular Biology (pp. 101-119). Springer, Cham.

Hallen, M. A., Martin, J. W., Ojewole, A., Jou, J. D., Lowegard, A. U., Frenkel, M. S., Gainza, P., Nisonoff, H.M., Mukund, A., Wang, S., Holt, G. T., Zhou, D., Dowd, E., & Donald B.R. (2018). OSPREY 3.0: Open-Source Protein Redesign for You, with Powerful New Features. Journal of Computational Chemistry, 39(30), 2494-2507.

Ojewole, A.*, Lowegard, A.*, Gainza, P., Reeve, S. M., Georgiev, I., Anderson, A. C., & Donald, B. R. (2017). OSPREY predicts resistance mutations using positive and negative computational protein design. In Computational Protein Design (pp. 291-306). Humana Press, New York, NY.

*These authors contributed equally

First Year Rotations

Donald Lab Rotation: I spent the Fall semester of 2013 in the Donald lab focused on Plasmodium falciparum dihydrofolate reductase. Plasmodium falciparum is a protozoan parasite that causes malaria in humans. Dihydrofolate reductase, or DHFR, is an enzyme that converts dihydrofolate into tetrahydrofolate. DHFR is crucial in the synthesis of purines, thymidylic acid, and certain amino acids. The project I worked on focused on utilizing OSPREY, the Donald Lab's primary toolkit for manipulating protein structures and making predictions. I used OSPREY here to attempt to retrospectively predict resistance mutations in DHFR.

Richardson Lab Rotation: I spent the Spring semester of 2014 in the Richardson lab looking at protein structure motifs. I utilized a database of the top 8000 PDB structures (maintained by the Richardson lab) to first focus on all hydrogen bonds present in the top 8000 structures. After pruning the database for only hydrogen bonds, I pruned further to search for a motif known as a Tyrosine corner. A Tyrosine corner is a motif where a Tyrosine sidechain hydrogen bonds with the mainchain residue at the T-2, T-3, T-4, or T-5 position relative to the Tyrosine. Through a series of MySQL queries, I was able to pull out several examples of these motifs. This work also helped in establishing a protocol for pulling out motifs of interest from the large databases maintained by the lab.

Oas Lab Rotation: My final rotation was over the Summer of 2014 and focused more on benchwork that I had never been exposed to as an undergrad. This rotation was crucial in exposing me to where data comes from and how it is collected. I spent the first half of Summer learning how to prep protein (specifically a double B domain of Protein A from S. aureus) from a plasmid all the way through a final protein sample. This sample was then used in an NMR relaxation experiment designed to determine the flexibility of the linker between the two B domains. The second half of the summer was spent focused on sequence analysis. I was given ~200 nucleic acid sequences for the protein A gene, each from a whole genome sequence for an individual isolate. These genes from the whole genomes were provided by the Fowler lab. Of these, ~150 were useful for comparing the protein sequences between the alpha-helical bundle domains of protein A.