Methods and Applications in Computational Protein Design
MASSACHUSETTS INST OF TECH LEXINGTON LINCOLN LAB
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In this thesis, we summarize our work on applications and methods for computational protein design. First, we apply computational protein design to address the problem of degradation in stored proteins. Specifically, we target cysteine, asparagine, glutamine, and methionine amino acid residues to reduce or eliminate a proteins susceptibility to degradation via aggregation, deamidation, and oxidation. We demonstrate this technique on a subset of degradation-prone amino acids in phosphotriesterase, an enzyme that hydrolyzes toxic organophosphates including pesticides and chemical warfare agents. Second, we introduce BroMAPA to DEEA, an exhaustive branch-and-bound search technique with enumeration. Given the same computational resources, we show how BroMAPA is able to solve large designs by efficiently dividing the search space into small, solvable sub-problems.
- Organic Chemistry