本研究發現擺動胺基酸支鏈加上活化中心氫鍵限制可以提高 enrichment
factor(EF)，使用 Directory of Useful Decoys (DUD)資料庫為基準，計算 CDK2
蛋白激酶，平均來說，同時擺動胺基酸支鏈加上活性中心氫鍵限制時，EF 可以
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擺動 2 個胺基酸支鏈、擺動 3 個胺基酸支鏈以及動 4 個胺基酸支鏈，來進行交叉
分子嵌合。我們發現，當與結晶小分子嵌合時，固定蛋白質將有較高的機會找到
最穩定構型，但與非結晶小分子嵌合部分，則發現隨著不同組合的可動胺基酸支
鏈數，其再現結果有些比固定蛋白質來的好。第三部分，我們使用相同的四部分
設定條件，加上活性中心氫鍵做限制，進行 1000 個小分子的虛擬篩選，顯示以
下幾項結果：(1)選擇擺動 Met1160、Glu1127、Ile1084 加上活化中心氫鍵做限
制的篩選效果最佳。(2)篩選數量範圍，前 10%的結果可有效找到具活性之分子，
因此我們篩選前 10%做為設定較有效率。(3)根據本篇研究所挑選的 10 個 c-MET
晶構型中，我們選擇篩選結果較佳的 3CTJ 做為高速虛擬篩選的蛋白質構型。第
四部分，我們使用分子嵌合方法來搜尋新的 c-MET 抑制劑。我們以 Lipinski 所
提出的藥物篩選依據為基準，篩選美國 ZINC 化學資料庫，挑選出 40 萬個分子，
並根據第三部分的三項設定條件，來進行高速虛擬篩選。最後篩選出 10 個分子
化合物做為建議之抑制劑，並找出前 5 名小分子的結合模式。最後，本研究 c-Met
部分利用可動胺基酸支鏈加上活性中心附近氫鍵做限制的設定，來找出較為有效
的 c-MET 高速篩選方式，以得到更精準的篩選結果。經由最後篩選所得的分子，
將有助於實驗學家測試抑制效果時的優先考量次序，進而幫助實驗學家設計
c-MET 抑制劑。
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