Molecular Dynamic Simulation of the Porcine Pancreatic Lipase in Non-aqueous Organic Solvents
Molecular Dynamic Simulation of the Porcine Pancreatic Lipase in Non-aqueous Organic Solvents
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DOI：
10.3389/fbioe.2020.00676
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发表时间：
2020-07-14
影响因子：
5.7
通讯作者：
Zhu, Jie
中科院分区：
文献类型：
--
作者：
Chen, Zi-Shi;Wu, Yi-Da;Zhu, Jie
本文通过分子动力学（MD）模拟研究了猪胰脂肪酶（PPL）在二甲亚砜（DMSO）、丙二醇（PRG）和乙醇（EtOH）三种非水有机溶剂中的构象稳定性。比较研究了PPL在各种有机溶剂中的均方根偏差(RMSD)、回转半径(Rg)、溶液可及表面积(SASA)、径向分布函数(RDF)、氢键(H-bond)、拉马钱德兰图分析、二级结构和酶底物亲和力。结果表明，三种溶剂中PPL的主链和活性口袋RMSD以及亲水性ASA随着溶剂LogP的增加而增加，而溶剂与PPL之间的Rg、疏水性ASA以及H-键减少。在这三种有机溶剂中，DMSO 是一种更好的溶剂，与 PRG 和 EtOH 相比，PPL 可以在其中松散和延伸，并在 DMSO 中保留其天然主链。此外，Ramachandran 图分析表明 DMSO 中的 PPL 结构质量高于 PRG 和 EtOH 中的 PPL 结构质量。此外，分子对接结果表明，DMSO 中的 PPL 表现出最高的酶-底物亲和力。
This paper investigates the conformational stability of porcine pancreatic lipase (PPL) in three non-aqueous organic solvents, including dimethyl sulfoxide (DMSO), propylene glycol (PRG), and ethanol (EtOH) through molecular dynamic (MD) simulation. The root mean square deviations (RMSDs), radius of gyration (Rg), solution accessible surface area (SASA), radial distribution function (RDF), hydrogen bond (H-bond), Ramachandran plot analysis, secondary structure, and enzyme substrate affinity of the PPL in the various organic solvents were comparatively investigated. The results showed that the backbone and active pocket RMSD, and hydrophilic ASA of PPL in three solvents increase with the increase in the solvent LogP, while the Rg, hydrophobic ASA, and H-bond between the solvent and PPL decrease. Among the three organic solvents, DMSO acts as a better solvent, in which the PPL can be loose and extended, and retains its native backbone in DMSO compared to PRG and EtOH. Moreover, Ramachandran plot analysis indicated that the PPL structure quality in DMSO was higher than that in PRG and EtOH. Also, the molecular docking results showed that PPL in DMSO exhibited the highest enzyme-substrate affinity.