Part 1: Methods and theoretical concepts: thermodynamic and kinetic aspects of the folding and self-assembly of proteins; folding of peptide fragments in water solution - implications for initiation of protein folding; determination of protein structures by NMR - approaches towards extending the limits; new developments in protein crystallography; a computational tool for structural biology - crystallographic refinement by simulated annealing; knowledge-based protein modelling and design; computer aided protein design - methods and applications; computer simulations applied to site specific mutagenesis and ligand binding - the use of free energy perturbation methods. Part 2 Protein design with (industrial) enzymes: three dimensional structure determination of proteins in PERI; engineering of RNase T1; tertiary structure of xylanase and estimation of active sites by site directed mutegenesis; modification of milk-clotting aspartic proteases, chymosin and mucor rennin; towards the construction of new proteins; lacate dehydrogenase - effect of amino acid changes of properties; protein engineering of human Lysozyme; design and structures of disulfide containing subtilisin variants. Part 3 Protein design with biological response modifiers, including antibodies and protease inhibitors: design of novel insulins with changed self-association and ligand binding properties; human glycoproteins and derived variants from recombinant mammalian cell lines; the crossover linker - mechanisms and applications in gene modification; structure-function relationship in parathyroid hormone; structural and functional aspects of protein - protein interaction as studied through crystal structure of subtilisin complexed with its trapped substate SS1; genetic engineering of protease inhibitors, a1-antitrypsin and hirudin; design of efficient human leukocyte elastase inhibitors - variants of human pancreatic secretory trysin inhibitor; characterization of engineered proteins - some critical reflections.
