冷冻水环境中限制作用对蛋白质稳定性的影响
Confinement effects on protein stability in a freezing water environment
AI总结：
研究蛋白质在冷冻水环境中的行为，用分子动力学模拟，通过验证液固转变、主成分分析等揭示冰形成对蛋白质构象空间的影响及水结构对蛋白质稳定性的作用。
AI中文摘要：
理解蛋白质在低温下的行为仍是生物物理学的核心挑战，对冷变性和冷冻保存有直接影响。虽对过冷液体中蛋白质冷变性研究广泛，但嵌入生长冰晶格中蛋白质行为难以实验获取。本文用显式捕捉冰Ih形成的分子动力学模拟，表征酵母铁硫蛋白（Yfh1）在水环境结晶时的构象动力学。通过四个独立冰种复制品和三个温度下的液态水对照，验证液固转变。主成分分析等揭示溶剂结晶显著重塑可及构象空间。对溶剂可及表面积等的补充分析表明溶剂驱动蛋白质 - 水相互作用重组。结果表明低温下蛋白质行为不仅受温度影响，还受周围水的结构组织影响，冰形成通过限制构象采样同时保留甚至致密化界面水化层，突出水结构在冷冻条件下对蛋白质稳定性的决定作用。
英文摘要：
Understanding how proteins behave at low temperatures remains a central challenge in biophysics, with direct implications for cold denaturation and cryopreservation. While cold denaturation of proteins in the supercooled liquid regime has been studied extensively, the behavior of a protein embedded in a growing ice lattice remains largely inaccessible to experiments. Here we use molecular dynamics simulations that explicitly capture ice Ih formation to characterize the conformational dynamics of yeast frataxin (Yfh1) as its aqueous environment crystallizes. Using four independent ice-seeded replicas and liquid-water controls at three temperatures, we first validate the liquid-solid transition through convergent changes in solvent density, potential energy, and local bond-order parameters (W4, W6). Principal component analysis (PCA), dihedral PCA (dPCA), and free-energy landscapes then reveal that crystallization of the solvent markedly reshapes the accessible conformational space, shifting it from a continuous, highly connected regime in liquid water toward a discretized landscape dominated by confined states. Complementary analyses of solvent-accessible surface area (SASA), radius of gyration, and hydrogen bonding indicate a solvent-driven reorganization of protein-water interactions: although first-shell water remains liquid-like, its surface density increases under freezing, while conformational sampling contracts. Together, these results indicate that protein behavior at low temperatures is governed not by temperature alone but by the structural organization of the surrounding water. By imposing geometrical constraints on the solvent, ice formation restricts conformational sampling while preserving -- and even densifying -- the interfacial hydration layer, highlighting the role of water structure as a determinant of protein stability under freezing conditions.
