A 3D-structural model of memapsin 2 protease generated from theoretical study

Aim: To build a 3D structural model of memapsin 2 (M2) protease for theoretical study and drug design. Methods: Structural alignment was performed based on multiple and pairwise sequence alignment of three templates. After the initial model was generated, energy minimization was completed by applying molecular mechanics method. Molecular dynamics (MD) technique was used to do further structural optimization. Results: The 3D structural model of memapsin 2 was constructed. The model is reasonable according to several validation criteria. The active-site motifs of M2 are structurally supported by a beta-sheet rich domain and linked together with this domain through alpha helices. Tyr132 contained in beta-hairpin is a general characteristic of aspartic protease. The Calpha atom superimposing result is a direct verification that M2 is structurally unique but still belongs to the aspartic protease superfamily. Conclusion: The 3D-structure model from our study is informative to guide future molecular biology study about M2 and drug design based on database searching. 目的:通過理論方法建立M2蛋白酶的三維結構模型。方法:基于模板進行多重序列聯配和結構聯配建立M2蛋白酶的初始結構模型,對初始模型進行分子力學和分子動力學優化,用多種評價方法對所得結構進行合理評價。結果:得到了M2蛋白酶的三維結構模型,合理性評價結果表明該結構模型正確,M2蛋白酶的催化活性位點與天冬氨酸蛋白酶相似,區別在于與活性位點相鄰的結構域的構象不同。結構保守區α碳原子疊合結果說明M2蛋白酶與其他天冬氨酸蛋白酶具有相同的生物進化來源。結論:M2蛋白酶的結構模型可以為進一步的分子生物學實驗提供有益的參考,也可以此模型為基礎進行數據庫篩選和藥物分子設計。