β-secretase (BACE) is an important protease in the pathogenesis of Alzheimer’s disease. A set of 38 novel inhibitors of BACE were subjected to three-dimensional
quantitative structure-activity relationship (3D QSAR) studies using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches. The structures of these inhibitors were generated theoretically, and the conformations used in the 3D QSAR studies were defined by docking them into the known structure of beta-secretase 1 receptor through the GOLD programs. Some of the parameters used in these docking programs were selected by docking an X-ray ligand into the receptor and comparing the Root-Means-Square Difference (RMSD) computed between the coordinates of the X-ray and docked structure. 38 BACE inhibitors were performed using two methods: First, traditional 3D QSAR and Catalyst were performed. Second, using the Catalyst pharmacophore features to modify the multiple linear expression of CoMSIA were expect to acquire more accurate multiple regression.

β-secretase（簡稱BACE）在阿茲海默症病程的進展當中扮演非常重要的蛋白酶。此研究結合了3D構效關係理論和統計方法，其中包含了比較分子場分析和比較分子相似因子分析，針對38個BACE的抑制劑作分析，試圖找出合理且具有可信度之藥效活性基團的分布。此研究結合了3D構效關係理論和統計方法，其中包含了比較分子場分析和比較分子相似因子分析，針對38個BACE的抑制劑作分析，試圖找出合理且具有可信度之藥效活性基團的分布。這一系列抑制劑的結構會嚴謹地由GOLD這套軟體根據基因演算法計算出配體與受體交互作用後最有可能的構形，而3D構效關係方法再利用這些構形進行運算的工作。將具有X-ray結構的抑制劑嵌合至受體（BACE）中，嵌合所得之構形再與原本X-ray結構的構形作方均根差異的比對，而在計算過程中所設定的參數將保留作為其它抑制劑與受體嵌合時的參考。將具有X-ray結構的抑制劑嵌合至受體（BACE）中，嵌合所得之構形再與原本X-ray結構的構形作方均根差異的比對，而在計算過程中所設定的參數將保留作為其它抑制劑與受體嵌合時的參考。38個BACE的抑制劑主要會經由兩種方式來分析：首先，使用傳統的3D構效關係分析方法和Catalyst找出適當的藥效基團分布；再將Catalyst所得到之藥效基團特性結合CoMSIA的複回歸分析，期望找出能夠更準確地預測藥物活性的複回歸方程式。

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