本論文針對對稱性類鴉片胜肽分子biphalin(Tyr-D-Ala-Gly-Phe-NH)2及經修飾後的biphalin相關衍生物，以分子動力學模擬進行分子活性結構與藥效基團之研究。Biphalin分子是一合成的鎮痛藥分子，研究得知其不但具有高藥效，且在長期使用後副作用低，因此本論文利用分子動力學模擬方法，使用生醫軟體Gromacs 3.3.3進行為時50奈秒的模擬，設定兩種不同初始結構的biphalin分子，更以biphalin單邊修飾物(Tyr-D-Ala-Gly-Phe-NH-NH2)在相同環境下模擬後做比較。結果顯示兩種分子在扭轉角分析下某些特定角度有明顯不同，推論為與受體結合能力高低有關。另一方面，就統計概念探討其藥效特徵，其中顯示biphalin只要單側即能與受體結合，再進一步與單邊修飾物比較，藉此定義藥效基團，另外再以principle component analysis之方法，研究此兩種分子的主要運動模式，得到兩者皆是以open-close運動為主。未來將會繼續研究Biphalin修飾分子如環狀修飾物等，以進一步整理其共有活性結構。

My master thesis exploited molecular dynamics simulation method in discovering specific conformations of potential analgesic opioid peptides. Biphalin (Tyr-D-Ala-Gly-Phe-NH)2 is a synthetic peptide reporting with high potency as well as low side effects. In order to derive pharmacophore, which defines the minimum necessary structural characteristics a molecule must possess, of the peptide with the aim of receptors binding by molecular dynamics simulation was now investigated. I applied a 50 nano-second simulation of three cases using biomolecular software Gromacs 3.3.3. On the other hand, considering the instinct flexible structure of peptides, the biphalin analog (Tyr-D-Ala-Gly-Phe-NH-NH2) and different initial structure of biphalin was taken as control groups in identical simulation environments. The results showed that two kinds of molecules in the torsion angle for analysis, there are obviously different from some specific point of view, the inference with binding level of the receptor-binding capacity. On the other hand, the statistical concepts to explore its efficacy characteristics, which show only one side that is able to biphalin receptor binding, further comparison with the unilateral modification of materials, so as to define pharmacophore groups, with an additional order to principle component analysis of the method to study these two molecules in the main mode, are both based on open-close movement as major. The future study will investigate the structural characteristics and pharmacophore model of other biphalin derivatives such as cyclic biphalin analogues.

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