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

化学变化经常用全局术语来讨论，反应的焓就是一个典型的例子。在化学领域，人们也常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预期影响该大分子的远程区域。这种局部特征可以借助分子中原子理论 (AIM) 在分子内单个化学键或原子的水平上进行讨论。该理论分析了电子密度的 3D 形貌，从中推导出表征该密度的拓扑。电子密度可以通过理论计算来计算，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着改进，实验学家和理论家开始研究系统沿反应坐标演化的过程。此类研究对计算的要求更高，因为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孤立的关键点。随着系统从反应物通过过渡态演变为产物，原子和键特性的演变是本提案的主题，这是一个新兴且令人兴奋的研究领域。这项研究将揭示关键生化过程和反应的反应性、动力学和热力学，例如：（1）“ATP水解活化能的原子贡献”，旨在了解ATP如何储存和释放化学势能，以及Mg2催化该分子反应的模式，这些反应是维持生命所必需的。 （2）“核糖体内肽键形成机制”，旨在阐明核糖体活性位点内部肽键形成机制。 (3)“Field Effects on Löwdin Mechanism of Spontaneous Mutation”，旨在了解外部场影响遗传物质转录或复制之前DNA碱基对内质子跳跃所带来的基因突变率的机制。

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.