Molecular dynamics study of the mechanical properties of foldamers and the metal specificity of an isatin hydrolase
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Abstract
This thesis presents a theoretical investigation of the mechanical properties of foldamers and the metal specificity of an isatin hydrolase. In the first part, force-probe molecular dynamics simulations are applied to the study of the mechanical unfolding pathway of small oligomers adopting helix conformations. The detailed investigation of a model β-peptide demonstrates how molecular dynamics simulations can be used for revealing conformational and kinetic information of the unfolding pathway of oligomers. The statistical analysis of several hundreds of unfolding events and the comparison between different systems leads to the identification of the main determining structural factors of the unfolding pathway of the studied oligomers. Based on this findings, a series of rules for the prediction of the unfolding pathway of short oligomers are proposed. In the second part, the experimental observed metal specificity of an isatin hydrolase is investigated, using quantum mechanics and quantum- /molecular mechanics calculations. The metal specificity is explained based on the conformation adopted by the enzyme’s binding site with different metal ions and the hydrolysis reaction mechanism. Finally, the mechanism of the catalytic reaction with manganese is revealed using metadynamics simulations.