MODELING OF STRUCTURE OF AN INTEGRAL MEMBRANE PROTEIN AQUAPORIN

水是所有活细胞和它们的生命的基本成分 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期间，例如 调节体温，排毒，消化， 呼吸、循环和神经动态平衡。水通道蛋白-1(AQP1) 是一种完整的膜蛋白，其功能是作为一种特殊的 构成活性导水通道[92，93]。我们是 从人红细胞中预测AQP1结构的尝试 通过分级结构预测的膜[94] 接近。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 生物化学和生物化学的实验约束下的方法 光谱数据。人红细胞AQP1由269个氨基酸组成 形成六个跨膜螺旋的残基[94]。水病 进行分析以鉴定假定的跨膜 片段，然后通过多个序列独立验证 比对倾向分析和同源建模。一种共识 二级结构的赋值是从所有的组合中得出的 所使用的预测方法。的三维结构 通过比较建模建立了跨膜螺旋段。 然后将生成的三级结构聚合到一个 用分子动力学方法模拟了四元结构 通过在低分辨率提供的约束下的能量最小化 用电子显微镜测量三维电子密度图 [95]、定点突变和FT共振拉曼光谱，AS 以及残基的守恒。

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.