细胞周期蛋白D2同源模建及其与CDKs抑制剂对接研究  

Homologous modeling of cyclin D2 and docking with CDKs Inhibitors

作　　者：杜亚男 陈靖峰 先正平 曹洪玉[2,3] 唐乾[2,3] 王立皓 郑学仿[3] DU Ya-nan;CHEN Jing-feng;XIAN Zheng-ping;CAO Hong-yu;TANG Qian;WANC Li-hao;ZHENG Xue-ang(College of Environment and Chemical Engineering,Dalian University,Dalian 116622,China;College of Life Science and Biotechnology,Dalian University,Dalian 116622,China;Key experiments in bioorganic chemistry,Dalian University,Dalian 116622,China)

机构地区：[1]大连大学环境与化学工程学院,辽宁大连116622 [2]大连大学生命科学与技术学院,辽宁大连116622 [3]大连大学辽宁省生物有机化学重点实验室,辽宁大连116622

出　　处：《化学研究与应用》2023年第12期2871-2879,共9页Chemical Research and Application

基　　金：国家自然科学基金(Nos21601023);辽宁省教育厅基本科研项目(LJKQZ2021168)资助。

摘　　要：细胞周期蛋白D2(CyclinD2,CCND2)在细胞中的异常表达会诱发肿瘤等疾病,设计高选择性CCND2药物对抑制肿瘤具有重要意义。本文选用PDB数据库中与CCND2一级序列同源性最高的3G33为模板蛋白建模,通过Loop环区能量优化最终得到具有较高合理性和可信度的三维蛋白结构模型,最优模型VerifyScore为100.920,预测获得10个可能的活性位点。构建药物小分子的最低能量结构,将小分子对接至蛋白活性位点,根据对接模型确定不同药物小分子与蛋白活性位点的相互作用方式,筛选细胞周期依赖性激酶(CDKs)类似物作为药物小分子配体,实验结果对进一步研究CyclinD2的结构、功能具有理论指导意义,也为相关疾病的临床治疗奠定了理论基础。Abnormal expression of Cyclin D2(CCND2)in cells can induce cancer and malignancy.The design of highly selective CCND2 drugs is of great significance for tumor suppression.In this paper,3G33,which has the highest homology with CCND2 first-order sequence in PDB database,was selected as the template protein model.A three-dimensional protein structure model with high rationality and reliability was finally obtained by Loop region energy optimization.The Verify Score of the optimal model was 100.920,and 10 potential active sites were predicted.The minimum energy structure of small drug molecules was constructed,and the small molecules were docked to the protein active site.The interaction modes between different small drug molecules and the protein active sites were determined according to the docking models.The cell cycle-dependent kinases(CDKs)analogues were screened as the drug small molecule ligands.The experimental results provide theoretical guidance for further research on the struc-ture and function of Cyclin D2,and also lay a theoretical basis for clinical treatment of related diseases.

关 键 词：细胞周期蛋白D2 细胞周期依赖性激酶 同源建模 分子对接 

分 类 号：O641.3[理学—物理化学]