Hebbar Akshatha, Dey Poulumi, Vatti Anoop Kishore
Department of Chemical Engineering, Manipal Institute of Technology (MIT), Manipal Academy of Higher Education (MAHE), Manipal, India.
Department of Materials Science and Engineering, Faculty of Mechanical, Maritime and Materials Engineering (3mE), Delft University of Technology, Delft, Netherlands.
J Biomol Struct Dyn. 2024;42(23):13325-13333. doi: 10.1080/07391102.2023.2275178. Epub 2023 Nov 1.
The ability of neat deep eutectic solvents (DESs) to influence protein structure and function has gained considerable interest due to the unstable nature of enzymes or therapeutic proteins, which are often exposed to thermal, chemical, or mechanical stresses when handled at an industrial scale. In this study, we simulated a model globular protein, lysozyme, in water and six choline chloride-based DES using molecular dynamics simulations, to investigate the structural changes in various solvent environments, giving insights into the overall stability of lysozyme. Root mean square deviation (RMSD) and root mean square fluctuations (RMSF) of the C- backbone indicated that most DESs induced a less flexible and rigid lysozyme structure compared to water. The radius of gyration and end-to-end distance calculations pointed towards higher structural compactness in reline and levuline, while the structure of lysozyme considerably expanded in oxaline. Protein-solvent interactions were further analysed by hydrogen bonding interactions and radial distribution functions (RDF), which indicated a higher degree of lysozyme-hydrogen bond donor (HBD) interactions compared to lysozyme-choline hydrogen bonding. Surface area analysis revealed an overall % increase in total positive, negative, donor, and acceptor surface areas in malicine and oxaline compared to water and other DESs, indicating the exposure of a larger number of residues to interactions with the solvent. Reline, levuline, and polyol-based DESs comparatively stabilized lysozyme, even though changes in the secondary/tertiary structures were observed.Communicated by Ramaswamy H. Sarma.
由于酶或治疗性蛋白质的不稳定性质，在工业规模处理时它们经常受到热、化学或机械应力的影响，因此纯的深层共熔溶剂（DESs）影响蛋白质结构和功能的能力引起了人们的极大兴趣。在本研究中，我们使用分子动力学模拟在水和六种基于氯化胆碱的DES中模拟了一种模型球状蛋白质溶菌酶，以研究各种溶剂环境中的结构变化，从而深入了解溶菌酶的整体稳定性。C-主链的均方根偏差（RMSD）和均方根波动（RMSF）表明，与水相比，大多数DESs诱导溶菌酶结构的柔韧性和刚性降低。回转半径和端到端距离的计算表明，在reline和levuline中结构紧凑性更高，而在oxaline中溶菌酶的结构显著扩展。通过氢键相互作用和径向分布函数（RDF）进一步分析了蛋白质-溶剂相互作用，结果表明与溶菌酶-胆碱氢键相比，溶菌酶-氢键供体（HBD）相互作用的程度更高。表面积分析显示，与水和其他DESs相比，malicine和oxaline中总的正、负电荷、供体和受体表面积总体增加了%，这表明有更多的残基暴露于与溶剂的相互作用中。尽管观察到二级/三级结构发生了变化，但reline、levuline和基于多元醇的DESs相对稳定了溶菌酶。由Ramaswamy H. Sarma传达。
