Computational molecular modeling in peptide design: A dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy

• Main Authors: Yi-Ting Liu, 劉奕廷
• Other Authors: Yeng-Tseng Wang
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/49729322910841436344

碩士 === 高雄醫學大學 === 醫學系生物化學科碩士班 === 104 === This dissertation, studies the MDMX and MDM2 interactions with the peptide inhibitors related to the research of computer-aided drug design(CADD) by employing the molecular simulations approach. These results can help drug designers to improve their products for treating special diseases. Antibody drugs specifically recognize antigens. To date, antibody drugs have already been widely applied to treat formidable disease, such as cancer. Traditional antibodies design strategy is used to inject the mouse with the disease association antigen and mouse monoclonal antibodies (Mabs) are generated. Then the CDR regions of the Mabs are modified by molecular biology techniques. Then the best modified Mabs will be changed the scaffold to generate humanized monoclonal antibody, produce by hybridoma techniques. Thus, the traditional antibodies design strategy takes time as well as money. The peptide drugs are defined as molecules containing fewer than 50 amino acids. The advantages of peptides drugs are: (1) high potency and selectivity for disease targets; (2) potentially lower toxicity than small molecules and Low accumulation in tissues; (3) high chemical and biological diversity and (4) discoverable at peptide and or nucleic acid levels. Our results are shown in below: (1) develop a tenure can speed up simulation time and accuracy of the preferred computing strategy (2) predicitng the hot-spots residues of dual inhibitors of MDM2 and MDMX; (3) predicting the 3D models of MDMX and MDM2 with the peptide inhibitors. The results of this paper to develop a strategy calculated by adding Gaussian molecular dynamics, computational analysis by binding of MDM2 to verify and confirm this group has indeed been calculated strategy to accelerate the simulation time and preferred to maintain accuracy, and therefore this calculation method as a basis for analyzing the structure and mode dual inhibit binding MDM2 / MDMX peptides and MDM2 / MDMX between the final results of our analysis of the relationship between peptide binding and MDM2 / MDMX between the important amino acids, can as the future direction of the future development of peptide inhibitors.