No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

Antibodies are the fundamental agents of the immune system. The CDRs, or Complementarity Determining Regions act as the functional surfaces in binding antibodies to their targets. These CDR structures, which are peptide loops, are diverse in both amino acid sequence and structure. In 2011, we surveyed a database of CDR loop structures using the affinity propagation clustering algorithm of Frey and Dueck. With the growth of the number of structures deposited in the Protein Data Bank, the number of antibody CDRs has approximately tripled. In addition, although the affinity clustering in 2011 was successful in many ways, the methods used left too much noise in the data, and the affinity clustering algorithm tended to clump diverse structures together. This work revisits the antibody CDR clustering problem and uses five different clustering algorithms to categorize the data. Three of the clustering algorithms use DBSCAN but differ in the data comparison functions used. One uses the sum of the dihedral distances, while another uses the supremum of the dihedral distances, and the third uses the Jarvis-Patrick shared nearest neighbor similarity, where the nearest neighbor lists are compiled using the sum of the dihedral distances. The other two clustering methods use the k-medoids algorithm, one of which has been modified to include the use of pairwise constraints. Overall, the DBSCAN using the sum of dihedral distances and the supremum of the dihedral distances produced the best clustering results as measured by the average silhouette coefficient, while the constrained k-medoids clustering algorithm had the worst clustering results overall. / Computer and Information Science

This study focuses on the utilization of metal-dependent monoclonal antibodies for large-scale chromatography and addresses an aspect that has been cited to lower immunosorbent performance, namely "orientation" of antibodies on matrices. The antibodies used in this study, the "EDTAdependent" 7D7BlO and the "Ca²⁺ -dependent" HPC4 are directed against human Protein C (PC). The 7D7BI0 antibody was characterized in terms of its metaldependency and specificity. The region of PC (epitope) recognized by 7D7BlO was identified as the first 15 residues in the NH₂-terminal. Immunosorbents made with 7D7BI0 provided highly pure and functional PC. The "orientation" of the antibodies on matrices was addressed in two ways. In the first approach, performance of immunosorbents coupled through carbohydrate moieties were compared with immunosorbents coupled through peptide regions. Coupling via carbohydrate linkages, which is generally believed to be Fc-directed, did not have any advantage in terms of efficiency and recovery over coupling via peptide. / Ph. D.