| t-PA (tissue-type Plasminogen Activator), a Physiological activator of Fibrinolytic system in blood, is proved to have great effect for the treatment of common thrombosis. Currently, affinity chromatography with high selectivity has already been applyed to purify and isolate these macromolecules; however, rational design of affinity ligands with better protein stability is still challenging. In this thesis molecular simulations and other computational methods are used on protein-ligand interaction analysis and protein ligand design. We designed a Hydrogel Matrix modified with affinity ligand based on the interaction between t-PA and affinity group from Tetrapeptide QDES, which could be of potential use for t-PA purification.This paper is mainly composed of the following three parts:Chapter1:A brief introduction of the background and impotance of this work is given.Chapter2:a brief introduction of molecular dynamics simulations is presented.Chapter3:The adsorption-desorption dynamics of t-PA on Polyvinyl alcohol with affinity ligands intercepted from Tetrapeptide QDES were studied in detail. We found that the plane of t-PA where the S1pocket located has high affinity to the selected ligands. All three types of adsorption functional groups from Tetrapeptide QDES:-OH (Neutral),-NH3+(Positively charged), and-COO-(Negatively charged), have interaction with t-PA. The interaction energy was found to be significant in the case that the charged ligands were modified on the hydrogel (such as amidine and carboxyl), and in this case there would be more than one type of residue on the whole plane of t-PA which had adsorbed to charged ligands simultaneously. Therefore, the desorption of t-PA is observed as a gradual process. In addition, if the modified ligands were neutral, the interaction energy was very limited. The results obtained through the molecular dynamics calculations confirm the affinity ability difference of these three selected ligands. |
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