PROTON TRANSFERS IN PROTEINS

酶的催化机制经常需要 质子从一个残基转移到另一个残基。 此外该 跨膜质子梯度的积累与 其中质子沿着包含在其中的H-键合残基的链跳跃 跨膜蛋白 量子化学方法将用于 这个项目是为了调查的基本原则， 质子转移反应 作为三维结构的 蛋白质的种类繁多， H-键的几何形状，质子转移将研究各种 对残基，并为每对，一系列的系统 将考虑氢键几何形状的变化。 战略 首先要进行非常复杂的 包括大基组和电子相关的计算 在小型模型系统上以准确的方式提取 转移过程的基本性质。 以连续 阶段，模型系统将逐步扩大到更多 真实蛋白质残基的真实模型。 那庞大的身躯 从这些研究中获得的系统数据将用于帮助 理解各种质子化状态的方式 可以控制残留物。 可能机制 蛋白质内的构象变化可以偶联到 质子的“推动”将被彻底探索。 的影响 将通过比较质子浓度来检查过程中的pH值。 适当的各种质子化状态的转移性质 残基（例如-COOH与-COO-）。 蛋白质的作用 质子转移后的环境将通过以下方式进行监测： H键附近的带电和极性基团以及 结合介质对电荷分布的响应 在H键中。

The catalytic mechanisms of enzymes frequently requires the transfer of a proton from one residue to another. In addition, the buildup of proton gradients across membranes has been associated with proton hops along chains of H-bonded residues contained within transmembrane proteins. Quantum chemical methods will be used in this project to investigate the fundamental principles of the proton transfer reaction. As the three-dimensional structure of proteins makes for a wide diversity of different types and geometries of H-bonds, proton transfers will be studied for various pairs of residues and for each pair, a range of systematic variations in the H-bond geometry will be considered. The strategy of the project is such as to first carry out very sophisticated calculations including large basis sets and electron correlation on small model systems to extract in an accurate way the fundamental properties of the transfer process. In successive stages, the model systems will be progressively enlarged to more realistic models of true protein residues. The large body of systematic data obtained from these studies will be used to help understand means by which the protonation states of various residues can be controlled. Possible mechanisms by which conformational changes within the protein may be coupled to a "pushing" of a proton 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 effect of the protein environment upon the proton transfer will be monitored by including charged and polar groups in the vicinity of the H-bond as well as incorporating the response of the medium to the charge distribution within the H-bond.