首页|二氯甲烷脱卤酶中二氯甲烷和谷胱甘肽解离途径的表征

二氯甲烷脱卤酶中二氯甲烷和谷胱甘肽解离途径的表征

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二氯甲烷(DCM)脱卤酶是在多种环境和生物背景下参与二氯甲烷降解的关键酶.然而,对DCM脱卤酶的配体解结合途径的研究尚不清楚.为了深入地了解DCM和谷胱甘肽(GSH)在DCM脱卤酶中的结合位点和解离途径,采用随机加速分子动力学(RAMD)模拟,驱动DCM和GSH离开活性部位.利用Alphafold2预测蛋白结构,通过对接预测GSH和DCM在结合口袋中的构象.通过长时间的平衡模拟验证该蛋白配体复合物的结构.结果表明,GSH在三种主要途径中最常见,其中一种比另外两种更重要.此外,模拟观察到DCM有一条独特的逃逸途径,鉴定了每个通路的关键残基和蛋白螺旋.该结果可为后续研究DCM脱卤酶解离机理提供理论基础.
Characterization of the dissociation pathways of dichloromethane and glutathione in dichloromethane dehalogenase
Dichloromethane(DCM)dehalogenase stands as a crucial enzyme implicated in the degradation of methylene chloride across diverse environmental and biological contexts.However,the unbinding pathways of ligands from DCM dehalogenase remain unexplored.In order to gain a deeper understanding of the binding sites and dissociation pathways of dichloromethane(DCM)and glutathione(GSH)from the DCM dehalogenase,random accelerated molecular dynamics(RAMD)simulations were performed,in which DCM and GSH were forced to leave the active site.The protein structure was predicted using Alphafold2,and the conformations of GSH and DCM in the binding pocket were predicted by docking.A long equilibrium simulation was conducted to validate the structure of the complex.The results show that GSH is most commonly observed in three main pathways,one of which is more important than the other two.In addition,DCM was observed to escape along a unique pathway.The key residues and protein helices of each pathway were identified.The results can provide a theoretical foundation for the subsequent dissociation mechanism of DCM dehalogenase.

DCM dehalogenaseGSHAlphafold2RAMDunbinding pathways

高旭丹、张慧珠、梅晔

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精密光谱学国家重点实验室,华东师范大学物理与电子科学学院,上海,200241

上海纽约大学计算化学中心,上海,200062

山西大学极限光学协同创新中心,太原,030006

二氯甲烷脱卤酶 谷胱甘肽 Alphafold2 随机加速分子动力学 解结合途径

National Natural Science Foundation of ChinaOriental Scholars of Shanghai UniversitiesSupercomputer Center of East China Normal University(ECNU Public Platform for Innovation)

22073030001

2024

10.13232/j.cnki.jnju.2024.04.012

南京大学学报(自然科学版)
南京大学

南京大学学报(自然科学版)

CSTPCD北大核心
影响因子：0.756
ISSN：0469-5097
年,卷(期)：2024.60(4)