Optimizing Bayes error for protein structure model selection by stability mutagenesis.

Site-directed mutagenesis affects protein stability in a manner dependent on the local structural environment of the mutated residue; e.g., a hydrophobic to polar substitution would behave differently in the core vs.

Algorithms for selecting breakpoint locations to optimize diversity in protein engineering by site-directed protein recombination.

Protein engineering by site-directed recombination seeks to develop proteins with new or improved function, by accumulating multiple mutations from a set of homologous parent proteins. A library of hybrid proteins is created by recombining the parent proteins at specified breakpoint locations; subsequent screening/selection identifies hybrids with desirable functional characteristics. In order to improve the frequency of generating novel hybrids, this paper develops the first approach to explicitly plan for diversity in site-directed recombination, including metrics for characterizing the diversity of a planned hybrid library and efficient algorithms for optimizing experiments accordingly.

Hypergraph model of multi-residue interactions in proteins: sequentially-constrained partitioning algorithms for optimization of site-directed protein recombination.

Relationships among amino acids determine stability and function and are also constrained by evolutionary history. We develop a probabilistic hypergraph model of residue relationships that generalizes traditional pairwise contact potentials to account for the statistics of multi-residue interactions. Using this model, we detected non-random associations in protein families and in the protein database.

Probabilistic cross-link analysis and experiment planning for high-throughput elucidation of protein structure.

Emerging high-throughput techniques for the characterization of protein and protein-complex structures yield noisy data with sparse information content, placing a significant burden on computation to properly interpret the experimental data. One such technique uses cross-linking (chemical or by cysteine oxidation) to confirm or select among proposed structural models (e.g.