MODELING OF STRUCTURE OF AN INTEGRAL MEMBRANE PROTEIN AQUAPORIN

水是所有活细胞的基本组成部分， 细胞外环境 水进出细胞的运输 发生在各种重要的细胞功能， 调节体温，排除毒素，消化， 呼吸循环和神经稳态 水通道蛋白1 是一种完整的膜蛋白，作为一种特异性的， 水的流动性[92]。 我们 试图预测人红细胞AQP1的结构 膜[94]通过分级结构预测 approach. 在这种方法中，分子动力学模拟和能量 最小化与常规结构预测相结合 方法的实验限制来自生物化学和 光谱数据 人红细胞AQP1由269个氨基酸组成， [94]这是一个六个跨膜螺旋。 亲水性 进行分析以鉴定推定的跨膜 片段，然后通过多个序列独立验证 比对倾向分析和同源性建模。 共识 二级结构的分配来自所有 使用的预测方法。 三维结构， 通过比较建模构建跨膜螺旋片段。 然后将所得的三级结构聚集成 四级结构，通过分子动力学模拟， 通过在低分辨率提供的约束下的能量最小化 电子显微镜三维电子密度图 [95]定点诱变和FT共振拉曼光谱，如 以及残基的保存。

Water is an essential component of all living cells and their extracellular surroundings. Transport of water in and out of cells occurs during a variety of important cellular functions such as regulation of body temperature, elimination of toxins, digestion, respiration, circulation, and neural homeostasis. Aquaporin-1 (AQP1) is an integral membrane protein that functions as a specific and constitutively active water conducting channel [92, 93]. We are attempting to predict the structure of AQP1 from human erythrocyte membranes [94] by means of a hierarchical structure prediction approach. In this approach molecular dynamics simulations and energy minimization are combined with conventional structure prediction methods under experimental constraints derived from biochemical and spectroscopical data. AQP1 from human erythrocyte is composed of 269 residues [94] that form six transmembrane helices. Hydropathy analysis was performed to identify the putative transmembrane segments, which were then independently verified by multiple sequence alignment propensity analyses and homology modeling. A consensus assignment for secondary structure was derived from combination of all the prediction methods used. Three dimensional structures for transmembrane helical segments were built by comparative modeling. The resulting tertiary structures were then aggregated into a quaternary structure through molecular dynamics simulations followed by energy minimization under constraints provided by a low resolution three dimensional electron density map measured by electron microscopy [95], site directed mutagenesis and FT Resonance Raman spectra, as well as conservation of residues.