Excursions of the electron density over the potential energy landscape in the absence and presence of external perturbations

化学变化经常用全球术语来讨论，反应的热焓就是一个典型的例子。在化学中，人们也经常对局部变化感兴趣。例如，涉及巨型多肽中氨基酸侧链的反应不能期望影响这种大分子的偏远区域。借助于分子中原子理论(AIM)，可以在分子内单个化学键或原子的水平上讨论这种局域特征。该理论分析了电子密度的三维形貌，并由此推导出表征该密度的拓扑结构。电子密度可以从理论计算中计算出来，也可以在X射线衍射实验中观察到。最近，由于实验技术和计算机速度的显著提高，实验学家和理论家开始研究系统沿反应坐标的演化。这种类型的研究对计算的要求要高得多，因为人们现在必须处理通常在数十或数百个点采样的整个景观，而不是势能景观上的少数几个孤立的临界点。随着体系从反应物到产物从反应物到产物再到过渡态，原子和键性质的演变是这一提议的主题，这是一个新兴而令人兴奋的研究方向。这项研究将阐明关键生化过程和反应的反应性、动力学和热力学，例如：(1)“原子对ATP水解激活能的贡献”，旨在了解化学势能是如何在ATP中储存和释放的，以及Mg2催化该分子反应的方式，这些反应是维持生命不可或缺的。(2)《核糖体内多肽键的形成机理》，旨在阐明核糖体活性部位内多肽键的形成机理。(3)“场对L自发突变机制的影响”，旨在了解外场影响遗传物质转录或复制前DNA碱基对内质子跳跃所引起的遗传突变率的机制(S)。

Chemical change is often discussed in global terms, the enthalpy of a reaction being a typical example. In chemistry, one is also often interested in local change. A reaction involving the side chain of an amino acid in a gigantic polypeptide cannot, for example, be expected to affect remote regions of this macromolecule. This local character can be discussed at the level of individual chemical bonds or atoms within a molecule with the help of the theory of atoms in molecules (AIM). This theory analyzes the 3D topography of the electron density from which the topology characterizing this density is deduced. The electron density can be computed from theoretical calculations but can also be observed in X-ray diffraction experiments. Very recently, and due to considerable improvements in experimental techniques and in computer speeds, experimentalists and theoreticians began to study systems as they evolve along the reaction coordinate. This type of study is much more computationally demanding since instead of a handful of isolated critical points on the potential energy landscape, one now has to deal with the entire landscape typically sampled at tens or hundreds of points. The evolution of atomic and bond properties as the system evolves from reactants to products through the transition state is the subject of this proposal, an emerging and exciting line of research. This research will shed light on reactivity, kinetics, and thermodynamics of key biochemical processes and reactions, e.g.: (1) "Atomic Contributions to the Activation Energy of the Hydrolysis of ATP", aiming at understanding how chemical potential energy is stored in and released from ATP and the mode by which Mg2+ catalyzes the reactions of this molecule, reactions that are indispensible in sustaining life. (2) "The Mechanism of the Peptide Bond Formation in the Ribosome", aiming at elucidating the mechanism of formation of the peptide bond inside the active site of the ribosome. (3) "Field Effects on Löwdin Mechanism of Spontaneous Mutation", aiming at understanding the mechanism(s) by which external fields influence the rate of genetic mutations brought about by the proton hopping within DNA base pairs prior to transcription or replication of the genetic material.