Biswas Samadrita, Pathak Nilavra, Sutherland Leah, Chen Alan A, Welch John T
Department of Chemistry, University at Albany, State University of New York, 1400 Washington Ave, Albany, NY 12222, USA.
Marketing Data Science, Expedia Group, 350 Fifth Ave, 7220, New York 10118, USA.
Phys Chem Chem Phys. 2025 Jan 22;27(4):2001-2010. doi: 10.1039/d4cp02654c.
The influence of aqueous solutions of 2-(tetrafluoro(trifluoromethyl)-λ-sulfanyl-ethan-1-ol (CFSF-ethanol) and 2,2,2-trifluoroethanol (TFE) on the secondary structure of melittin was studied using circular dichroism (CD) and molecular dynamics (MD) simulations. In water, melittin transitions into a random coil. However, upon addition of even as little as 1% by volume of CFSF-ethanol, the secondary structure of melittin stabilizes as a helix. Contrarily, the addition of 40% by volume of TFE is required for the greatest helicity. Fluoroalcohols stabilize melittin's hydrophobic side chain residues, thereby enhancing the helical structure. Locally alcohol concentrations approach nearly 70-90% in the near vicinity of the hydrophobic side chains increasing hydrophobic interactions and reducing water-peptide hydrogen bonding. Using the molecular mechanics-Poisson Boltzmann surface area method (MMPBSA), the free energy of binding between the peptide and fluoroalcohols highlighted the role of nonpolar residues in stabilizing the secondary structure. Secondary structure content analysis (SESCA) validated the simulation results, confirming CFSF-ethanol as an effective, eco-friendly enhancer of helicity at low concentrations. The far UV circular dichroism (CD) spectrum of melittin in solutions containing TFE corroborates previous findings and likewise affirms that the addition of CFSF-ethanol to an aqueous solution can enhance helicity. The agreement between the experimental and calculated helicities highlights the potential of CFSF-ethanol. This study offers insights into peptide stabilization by fluoroalcohols, with implications for peptide-based therapeutic design.
利用圆二色性（CD）和分子动力学（MD）模拟研究了2-（四氟（三氟甲基）-λ-硫烷基-乙醇（CFSF-乙醇）和2,2,2-三氟乙醇（TFE）的水溶液对蜂毒肽二级结构的影响。在水中，蜂毒肽转变为无规卷曲。然而，即使加入低至1%（体积）的CFSF-乙醇，蜂毒肽的二级结构也会稳定为螺旋结构。相反，需要加入40%（体积）的TFE才能达到最大螺旋度。含氟醇使蜂毒肽的疏水侧链残基稳定，从而增强螺旋结构。在疏水侧链附近，局部醇浓度接近70-90%，增加了疏水相互作用并减少了水-肽氢键。使用分子力学-泊松玻尔兹曼表面积法（MMPBSA），肽与含氟醇之间的结合自由能突出了非极性残基在稳定二级结构中的作用。二级结构含量分析（SESCA）验证了模拟结果，证实CFSF-乙醇在低浓度下是一种有效、环保的螺旋度增强剂。含TFE溶液中蜂毒肽的远紫外圆二色性（CD）光谱证实了先前的发现，同样肯定了向水溶液中添加CFSF-乙醇可以增强螺旋度。实验和计算的螺旋度之间的一致性突出了CFSF-乙醇的潜力。这项研究为含氟醇对肽的稳定作用提供了见解，对基于肽的治疗设计具有启示意义。
