Design the optimal nucleic acid aptamer sequence with the specificity of specific cancer cell using molecular simulation

• Main Authors: Yu-Sheng Lin, 林雨聖
• Other Authors: Shin-Pon Ju
• Format: Others
• Language: zh-TW
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/7pd58u

碩士 === 國立中山大學 === 機械與機電工程學系研究所 === 107 === Despite advances in drug development and medical technology, cancer is still the top 10 cause of death in China. If cancer cells appear in the body, they can be detected immediately and treated appropriately, which can effectively reduce the chance of cancer and cancer death. In terms of cancer cell identification technology, Aptamer can be used to identify specific protein target molecules on cancer cells, so as to know the existence of specific cancer cells. But as a result of using SELEX (system evolution of ligands by an exponential enrichment) technology, the screening of specific protein molecules target a specific aptamer, need a longer time and higher spending. To this end, a set of numerical methods were proposed in this study, with Epithelial cell adhesion molecule (EpCAM) on colorectal cancer as a specific protein target molecule, and the binding structure of EpCAM with the appropriate EpA sequence was analyzed to simulate the interactions of this compound in the experiment. In addition, a new global minimum search method named STUN-BH-DMD is proposed for the most stable structures between complexes. The methods are Stochastic tunneling (STUN), channel-hopping (BH), Molecular Dynamics (MD), and Discrete Molecular Dynamics (DMD). The results of this study showed that the residual segments of EpCAM mainly interacting with EpA were 25~130, 275~375 and 425~484, and the segments of EpCAM mainly interacting with EpCAM were close to the 3’-EpA. In addition, it was found that the bases of EpA mainly interact with hydrophilic residues on EpCAM.