在去除老鼠的基因的研究表明，缺失PTP1B蛋白質老鼠的胰島素敏感性明顯增加，並對肥胖有一定的抵抗作用，因此PTP1B被認為可用來設計治療第二型糖尿病藥物的標靶。隨著計算機科學的進步，利用電腦虛擬篩選來加速藥物的開發已慢慢成為趨勢，能有效的縮短研發的時間與經費，在國外藥廠已有不少成功的例子。本實驗採用直接性與間接性兩種虛擬藥物設計的方法，來篩選出PTP1B的有效抑制劑。首先找出直接性藥物設計軟體DOCK對PTP1B受體合理的參數，此參數所建立的模型在抑制劑活性排名的相關係數可達0.79，隨後則進行化學資料庫Maybridge的虛擬藥物篩選。另外一方面，建立間接性藥物設計軟體Catalyst對PTP1B抑制劑的藥效基團，相關係數達0.976，均方根平方值達0.868，接著針對由DOCK軟體篩選出的化合物作活性預測。除此之外，搭配XScore、PScore兩種評分函數，以及氫鍵的篩選方式，最後挑選出165個最具潛力的PTP1B先導藥物。

The research on the knock-out studies in mice manifests that the insulin resistance in those mice lacking for PTP1B protein would evidently increases and possesses the certain resistivity against obesity. Consequently, PTP1B is considered as the target for medicine designed to treat for Type II diabetes. With the progress in computational science, it is gradually becoming a trend to utilize the virtual screening method to accelerate the R&D in medication and effectively shorten the time and expense of R & D. In fact, there are not a few successful examples applied in foreign pharmacists. This experiment is in regard to adopting direct and indirect drug methods to screen the available inhibitor for PTP1B. First, it’s to find out the reasonable parameter computed through “DOCK” software of direct drug method towards the PTP1B receptor, the model based on the aforementioned parameter, which correlation can reach 0.79 in the activity ranks of inhibitor, then to proceed the virtual screening in “Maybridge” chemistry database. On the other hand, to establish the pharmacoophore which the so-called “Catalyst” indirect drug method software applied in screening PTP1B inhibitor, then reaching 0.976 correlation and 0.868 rms following this step, to make the activity predict on the compound screened by the DOCK software. In addition to this, assorting with two scoring function in terms of XScore and PScore, and the screening method of hydrogen bond, at last select 165 most potential lead compounds of PTP1B.

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