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.
Biopolymers. 2017 May;108(3). doi: 10.1002/bip.23009.
Thermal melting and recooling of AuIB, a neurotoxic conopeptide and a highly potent nonaddictive pain reliever is investigated thoroughly in water and an ionic liquid (IL) 1-butyl-3-methylimidazolium Chloride, [Im ][Cl] by classical molecular dynamics simulations. Structural evolution of AuIB in water and the IL is observed at different temperatures between 305 and 400 K, to explore how highly viscous ionic solvents affect the peptide structure as compared to conventional solvent water. At 305 K, unlike water, the coercive effect of IL frustrates AuIB secondary structural motifs significantly. As the temperature is raised, a very interesting IL induced conformational transition from 3 - to α-helix is noticed in the peptide, presumably triggered by a significant restructuring of the peptide H-bond network. The backbone length distributions of the peptide indicate that the IL induced conformational switching is accompanied by a reduction of the axial rise of the helical region, encompassing the residues Pro-6 to Ala-10. Further, we estimated the void space available to the peptide for its structural relaxation within the first solvation shell of ∼5 Å in water as well as in IL. A temperature increase by 100 K, opens up an estimated void volume of ∼70 Å , equivalent to the volume of approximately six water molecules, around the peptide in IL. Cooling simulations of AuIB point to the crucial interplay between thermodynamically favored AuIB conformers and their kinetic control. This study provides a comprehensive understanding of the ionic solvation of biomolecules reinforcing previous experimental findings.
通过经典分子动力学模拟，对神经毒性芋螺肽且高效非成瘾性止痛剂金环蛇毒素B（AuIB）在水和离子液体1-丁基-3-甲基咪唑鎓氯化物（[Im][Cl]）中的热熔化和再冷却过程进行了深入研究。在305至400 K的不同温度下观察了AuIB在水和离子液体中的结构演变，以探究与传统溶剂水相比，高粘性离子溶剂如何影响肽结构。在305 K时，与水不同，离子液体的强制作用显著破坏了AuIB的二级结构基序。随着温度升高，在肽中注意到一个非常有趣的由离子液体诱导的从β-折叠到α-螺旋的构象转变，推测是由肽氢键网络的显著重组引发的。肽的主链长度分布表明，离子液体诱导的构象转换伴随着螺旋区域轴向上升的减少，该螺旋区域包含从Pro-6到Ala-10的残基。此外，我们估计了在水和离子液体中约5 Å的第一溶剂化壳层内肽进行结构弛豫可用的空隙空间。温度升高100 K，在离子液体中肽周围会打开一个估计约70 Å的空隙体积，相当于大约六个水分子的体积。AuIB的冷却模拟表明热力学上有利的AuIB构象体与其动力学控制之间存在关键的相互作用。这项研究全面理解了生物分子的离子溶剂化，强化了先前的实验结果。
