Sajeevan Karuna Anna, Roy Durba
Department of Chemistry, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet Mandal, Hyderabad, Telangana, 500078, India.
Biophys Rev. 2018 Jun;10(3):769-780. doi: 10.1007/s12551-017-0391-2. Epub 2018 Jan 2.
The appearance of several disulfide bond isoforms in multiple cysteine containing venom peptides poses a significant challenge in their synthesis and purification under laboratory conditions. Recent experiments suggest that careful tuning of solvent and temperature conditions can propel the disulfide bond isoform equilibrium in favor of the most potent, native form. Certain aqueous ionic liquids (ILs) have proven significantly useful as solvents for this purpose, while exceptions have also been noted. To elucidate the molecular level origin behind such a preference, we report a detailed explicit solvent replica exchange molecular dynamics study of a conotoxin, AuIB, in pure water and four different aqueous IL solutions (~45-60% v/v). The ILs studied here are comprised of cations like 1-ethyl-3-methyl-imidazolium (Im) or 1-butyl-3-methyl-imidazolium (Im) coupled with either acetate (OAc) or chloride (Cl) as the counter anion. Our simulations unfold interesting features of the conformational spaces sampled by the peptide and its solvation in pure water and aqueous IL solutions. Detailed investigation into populations of the globular disulfide bond isoform of AuIB in aqueous IL solutions reveal distinct trends which might be related to the Hofmeister effect of the cation and anion of the IL and of specific interactions of the aqueous IL solutions with the peptide. In accordance with experimental observations, the aqueous [Im][OAc] solution is found to promote the highest globular isoform population in AuIB.
在多种含半胱氨酸的毒液肽中出现的几种二硫键异构体，给在实验室条件下合成和纯化它们带来了重大挑战。最近的实验表明，仔细调整溶剂和温度条件可以推动二硫键异构体的平衡，使其有利于最有效的天然形式。某些水性离子液体（ILs）已被证明作为用于此目的的溶剂非常有用，但也有例外情况。为了阐明这种偏好背后的分子水平起源，我们报告了一项关于芋螺毒素AuIB在纯水和四种不同水性离子液体溶液（~45 - 60% v/v）中的详细显式溶剂副本交换分子动力学研究。这里研究的离子液体由阳离子如1 - 乙基 - 3 - 甲基咪唑鎓（Im）或1 - 丁基 - 3 - 甲基咪唑鎓（Im）与醋酸根（OAc）或氯离子（Cl）作为抗衡阴离子结合而成。我们的模拟揭示了该肽在纯水和水性离子液体溶液中采样的构象空间的有趣特征。对AuIB在水性离子液体溶液中的球状二硫键异构体群体的详细研究揭示了不同的趋势，这可能与离子液体的阳离子和阴离子的霍夫迈斯特效应以及水性离子液体溶液与该肽的特定相互作用有关。与实验观察结果一致，发现水性[Im][OAc]溶液能促进AuIB中最高的球状异构体群体。
