Erschienen:
[Erscheinungsort nicht ermittelbar]: Universidade Nova de Lisboa. Instituto de Tecnologia Química e Biológica, 2010
Sprache:
Englisch
Identifikator:
Entstehung:
Hochschulschrift:
Dissertation, Universidade Nova de Lisboa. Instituto de Tecnologia Química e Biológica, 2010
Anmerkungen:
Beschreibung:
Dissertation presented to obtain the Doutoramento (Ph.D.) degree in Biochemistry at the Instituto de Tecnologia Qu mica e Biol ogica da Universidade Nova de Lisboa ; Computational protein design has achieved several milestones, including the design of a new protein fold, the design of enzymes for reactions that lack natural catalysts, and the re-engineering of protein-protein and protein-DNA binding speci city. These achievements have spurred demand to apply protein design methods to a wider array of research problems. However, the existing computational methods have largely relied on xed-backbone approaches that may limit the scope of problems that can be tackled. Here, we describe four computational protocols - side chain grafting, exible backbone remodeling, backbone grafting, and de novo sca old design - that expand the methodological protein design repertoire, three of which incorporate backbone exibility. Brie y, in the side chain grafting method, side chains of a structural motif are transplanted to a protein with a similar backbone conformation; in exible backbone remodeling, de novo segments of backbone are built and designed; in backbone grafting, structural motifs are explicitly grafted onto other proteins; and in de novo sca olding, a protein is folded and designed around a structural motif. We developed these new methods for the design of epitope-sca old vaccines in which viral neutralization epitopes of known three-dimensional structure were transplanted onto nonviral sca old proteins for conformational stabilization and immune presentation.(.)