Title: Water Dynamics around T0 vs. R4 of Hemoglobin from Local Hydrophobicity Analysis Show Chinese title

Title: 血红蛋白中T0与R4周围的水动力学行为来自局部疏水性分析

Abstract: The local hydration around tetrameric Hb in its T$_0$ and R$_4$ conformational substates is analyzed based on molecular dynamics simulations. Analysis of the local hydrophobicity (LH) for all residues at the $\alpha_1 \beta_2$ and $\alpha_2 \beta_1$ interfaces, responsible for the quaternary T$\rightarrow$R transition, which is encoded in the MWC model, as well as comparison with earlier computations of the solvent accessible surface area (SASA), makes clear that the two quantities measure different aspects of hydration. Local hydrophobicity quantifies the presence and structure of water molecules at the interface whereas ``buried surface'' reports on the available space for solvent. For simulations with Hb frozen in its T$_0$ and R$_4$ states the correlation coefficient between LH and buried surface is 0.36 and 0.44, respectively, but it increases considerably if the 95 \% confidence interval is used. The LH with Hb frozen and flexible changes little for most residues at the interfaces but is significantly altered for a few select ones, which are Thr41$\alpha$, Tyr42$\alpha$, Tyr140$\alpha$, Trp37$\beta$, Glu101$\beta$ (for T$_0$) and Thr38$\alpha$, Tyr42$\alpha$, Tyr140$\alpha$ (for R$_4$). The number of water molecules at the interface is found to increase by $\sim 25$ \% for T$_0$$\rightarrow$R$_4$ which is consistent with earlier measurements. Since hydration is found to be essential to protein function, it is clear that hydration also plays an essential role in allostery. Show Chinese abstract

Abstract: 四聚体Hb在其T$_0$和R$_4$构象亚状态周围的局部水合情况是基于分子动力学模拟分析的。 对位于$\alpha_1 \beta_2$和$\alpha_2 \beta_1$接口的所有残基的局部疏水性（LH）进行分析，这些接口负责四级结构的T$\rightarrow$R 转变，这在MWC模型中有所编码，同时与早期溶剂可及表面积（SASA）计算进行比较，表明这两个量测量的是水合的不同方面。 局部疏水性量化了界面处水分子的存在和结构，而“埋藏表面”则报告了溶剂可用的空间。 对于将Hb冻结在其T$_0$和R$_4$状态的模拟，LH与埋藏表面之间的相关系数分别为0.36和0.44，但如果使用95%置信区间，相关系数会显著增加。 LH 中 Hb 冻结和柔性在大多数界面残基上变化不大，但对少数选择的残基有显著改变，这些残基是 Thr41$\alpha$, Tyr42$\alpha$, Tyr140$\alpha$, Trp37$\beta$, Glu101$\beta$ (for T$_0$) 和 Thr38$\alpha$, Tyr42$\alpha$, Tyr140$\alpha$ (for R$_4$). 界面处的水分子数量被发现增加$\sim 25$ % 对于 T$_0$$\rightarrow$ R$_4$，这与以前的测量结果一致。由于水合被发现对蛋白质功能至关重要，显然水合在变构中也起着关键作用。