- 學位論文
PDST:蛋白質藥物的穩定性分析工具
PDST:Protein Drug Stability Tuner a web server to improve the stability of protein drug
摘要
蛋白質的穩定性是目前一個非常重要的研究重點，因為如果將其穩定性運用在蛋白質藥物的穩定性上，它可以決定藥物在體內的half life以及ADME(Absorption Distribution Metabolism Excretion)是否能夠達到最佳的效果。由於現在的許多藥物都是來自於protein或是peptide，針對這些藥物來進行修改並重組進而提高它的穩定度可以說是目前藥物學上最主要的挑戰之一。 進行蛋白質的穩定性修改可以從幾個方面來著手，例如：增加蛋白質內的ionic pair, hydrophobic interaction, hydrogen bond 等方面，因此，我們開發一個預測工具PDST (Protein Drug Stability Tuner)，它能夠預測及提供修改以及建議，藉由過去發展的蛋白質溫度穩定預測演算法：Temperature Index，再合併蛋白質半衰期穩定預測的：Instability Index，將其發展成Web介面的線上工具，提供使用者更準確的建議，我們更將序列置換的調控功能置入，發展成為一套完整的線上蛋白質藥物穩定性預測工具，可應用在蛋白質工程方面的修改分析。
並列摘要
The drug stability include half life and ADME are the important factors that influence the drug efficacy. However, the resource of a number of drugs are come from proteins or peptides, which can be modified and reconstituted for every purpose. How to increase protein drug stability is the main challenge for pharmaceutical study. There are many ways to solve the problem. For example, we can enhance ionic pair, hydrophobic interaction, and hydrogen bond etc. Our tool provides prediction and modification for protein stability by calculate Temperature Index (TI) and Instability Index (II). The Temperature Index (TI) was applied to determine the Tm (Melting Temperature) directly from protein sequences. PDST(Protein Drug Stability Tuner) is a novel web online tool to provide analyzing protein drug stability and suggesting the mutation by inputting primary sequences of proteins. PDST is a freely available at http://biotuner.bio.ncue.edu.tw/pdst.htm We integrate PDB and Drug Bank, these two databases calculate the TI and II of these proteins, test and verify the result of analyzing. In according to the result, we build up a new database to provide the query of stability of protein drug.