Methods and Applications in Computational Protein Design
Abstract
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 protein's 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 BroMAP/A* to DEE/A*, an exhaustive branch-and-bound search technique with enumeration. Given the same computational resources, we show how BroMAP/A* is able to solve large designs by efficiently dividing the search space into small, solvable sub-problems.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2010
- Accession Number
- ADA533265
Entities
People
- Jason C. Biddle
Organizations
- Massachusetts Institute of Technology