PROTON TRANSFERS IN PROTEINS

酶的催化机制通常需要 质子从一种残基转移到另一种残基。此外， 跨膜的质子梯度的积累与 其中含有氢键残基的链上有质子跃迁 跨膜蛋白。量子化学方法将被用于 这个项目是为了调查 质子转移反应。作为的三维结构， 蛋白质构成了种类繁多的不同类型和 氢键的几何构型，质子转移将研究不同的 残基对和每对残基的系统范围 氢键几何结构的变化将被考虑在内。战略 对项目的研究是这样的，首先要开展得很精细 包括大基组和电子关联在内的计算 在小模型系统上准确地提取 转移过程的基本属性。接连地 各阶段，模型系统将逐步扩大到更多 真实蛋白质残留物的真实模型。巨大的躯体 从这些研究中获得的系统数据将被用来帮助 理解各种不同的质子化状态 残留是可以控制的。可能的机制，通过它 蛋白质内的构象变化可能与一个 我们将彻底探索质子的“推动”。的影响 PH对过程的影响将通过与质子的比较来考察 不同质子态的转移性质 残基(例如-COOH与-COO-)。蛋白质的作用 将通过以下方式监测质子转移时的环境 氢键附近的带电基团和极性基团以及 结合介质对电荷分布的响应 在氢键中。

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.