PROTON TRANSFERS IN PROTEINS

质子的跨膜转运在细胞内起着不可或缺的作用， 生物能量转换过程，例如ATP形成。 证据 表明转运是通过氢键残基链进行的 包含在跨膜蛋白中。 运输是通过 一系列质子沿着氢键从一个残基转移到下一个残基， 锁链 量子化学方法将用于该项目， 研究质子在分子轨道上的迁移机制。 为 蛋白质的三维结构使得蛋白质的多样性 不同类型和几何形状的氢键，可能参与 链，质子转移的能量将计算各种对的质子转移的能量。 残基，并且对于每一对，氢键中的一系列系统变化 将考虑几何形状。 能量学的比较和分析 电子信息将导致详细了解 质子转移过程的基本原理。 这些分子特性 这是该过程的重要元素，例如极化率， 电负性等将被识别。 这些信息将使 对质子在基团间的转移也有预测 复杂的是要进行所需精度的计算。 计算将首先在由小模型组成的系统上进行 以便于应用非常精确的理论 技术，包括大基组和电子相关。 的 这些系统的简单性将允许将注意力集中在 质子转移过程的基础知识， 数据的解释。 模型的尺寸将逐渐 放大到每个蛋白质残基的更合适的表示， 确保计算的可靠性。 系统化的大型机构 从这些研究中获得的数据将用于确定结构 高效质子导管的要求。 可能机制 蛋白质内的构象变化可以与蛋白质内的构象变化的调节偶联。 质子流的速率将被彻底探索。 pH的影响 在该过程中将检查比较质子转移 适当残基的各种质子化状态的性质（例如， -COOH对-COO-）。 链的本地环境的方式 影响其传导特性将通过包括带电的 以及其附近的极性基团，并结合外部氢键 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.