PROTON TRANSFERS IN PROTEINS

质子在膜上的转移在 生物能量传递过程，如三磷酸腺苷的形成。证据 表明这种转运是通过氢键残基的链进行的 包含在跨膜蛋白中。传输是通过以下方式完成的 一系列的质子沿着氢键从一个残基转移到下一个残基。 链条。在这个项目中将使用量子化学方法来 研究了分子LE上的质子转移机制。作为 蛋白质的三维结构造就了广泛的多样性 可能参与的不同类型和几何构型的氢键 链，质子转移的能量学将被计算的各种对 残基和每对氢键的一系列系统变化 几何学将被考虑。能量学的比较与分析 电子信息将使您详细了解 质子转移过程的基本原理。这些分子特性 它们是该过程的重要元素，例如极化率， 电负性等将被确定。此信息将使 关于质子在基团之间转移的预测也很多 要接受所需精度的计算的复杂性。 计算将首先在由小模型组成的系统上执行 以便于应用非常精确的理论 包括大基组和电子关联在内的技术。这个 这些系统的简单性将使人们的注意力集中在 无竞争效应的质子转移过程基础 对数据的解释。模型的尺寸将逐渐增加到 放大到更合适的每个蛋白质残基的表示 确保计算的可靠性。体系化的庞大身体 从这些研究获得的数据将被用来确定结构 对高效质子管道的要求。可能的机制，通过它 蛋白质内的构象变化可能与蛋白质的调控有关 质子通量的速率将得到彻底的探索。酸碱度的影响 将通过比较质子转移来考察这一过程 适当残基的各种质子化状态的性质(例如 -COOH与-COO-)。链的本地环境的方式 对其导电性能的影响将通过包括带电 和其附近的极性基团以及结合外部氢键 在亲水环境中会发生的计算。

The translocation of protons across membranes plays an integral role in biological energy transduction processes such as ATP formation. Evidence suggests that the transport occurs via chains of H-bonded residues contained within transmembrane proteins. The transport is accomplished by a series of proton transfers from one residue to the next along H-bonds in the chain. Quantum chemical methods will be used in this project to investigate the proton translocation mechanism on a molecular le. As the three-dimensional structure of proteins makes for a wide diversity of different types and geometries of H-bonds that may participate in the chain, energetics of proton transfer will be calculated of various pairs of residues and for each pair, a range of systematic variations in the H-bond geometry will be considered. Comparisons of the energetics and analyses of electronic information will lead to a detailed understanding of the fundamentals of the proton transfer process. Those molecular properties that are important elements of the process such as polarizability, electronegativity, etc. will be identified. This information will enable predictions to be made about proton transfers between groups far too complex to be subjected to calculations of the required accuracy. Calculations will be performed first upon systems composed of small model of each residue to facilitate the application of very accurate theoretical techniques including large basis sets and electron correlation. The simplicity of these systems will allow a focusing of attention upon the basics of the proton transfer process without competing effects obscuring interpretation of the data. The sizes of the models will gradually be enlarged to more appropriate representations of each protein residue to ensure the reliability of the calculations. The large body of systematic data obtained from these studies will be used to determine the structural requirements of an efficient proton conduit. Possible mechanisms by which conformational changes within the protein may be coupled to modulation of the rate of proton flux will be thoroughly explored. The effects of pH upon the process will be examined by comparison of proton transfer properties of various protonation states of appropriate residues (e.g. -COOH vs. -COO-). The manner in which the local environment of the chain influences its conduction properties will be monitored by including charged and polar groups in its vicinity as well as incorporating external H-bonds into the calculations as would occur in a hydrophilic environment.