Theory of electronic processes in Molecules Subject to Intense X-ray Radiation: Towards Single-Molecule X-ray Diffraction Spectroscopy

要了解指导生物体内各种生化过程的机制，需要确定参与这些过程的生物分子(例如蛋白质)的结构。事实上，已经投入了大量的科学资源来试图揭示蛋白质的结构。在这条道路上取得的巨大成功极大地促进了我们通过设计新药与疾病作斗争的能力。在整个上个世纪，这一成功的标志是无数的诺贝尔物理学和化学奖。尽管目前的方法取得了显著的成就，但绝大多数生物分子的结构仍然是一个谜。这是因为，现有的主要X射线衍射技术的应用前提是正在研究的生物分子的结晶。事实证明，从蛋白质溶液中获得晶体，即几何有序的固体结构，通常是一项极其困难的任务。为了克服这一困难，一些研究人员建议用气相而不是晶体中的X射线衍射来分析蛋白质。这当然需要应用比目前可用的更强的X射线辐射，因为这样人们将试图获得单个生物分子的图像。幸运的是，世界各地的许多设施现在都在建造一种名为X射线自由电子激光的新的强大X射线源。有人提出，这些新光源产生的X射线辐射将足够强，可以在一次拍摄中拍摄出单个蛋白质分子的图像。这种方法的主要问题是，产生目标分子图像的辐射也会摧毁目标分子。单分子X射线衍射的新方法的命运取决于X射线-分子相互作用的两个基本后果之间的微妙平衡：辐射的衍射和分子的分解。中心问题是设计这样一种辐射脉冲，它足够强，足够长，可以提供足够质量的衍射图，但仍然足够短，不会导致分子在脉冲作用期间解体。只有当人们能够详细了解分子分解的所有可能的机制，并最终在计算机模拟中对其进行建模时，才有可能设计这样的脉冲。本提案的中心目标正是：对在强X射线作用下导致分子解体的电子过程进行理论研究，并在详细了解潜在物理机制的基础上对这一过程进行计算机模拟。这些机制包括X射线辐射对分子的电离以及电离事件后剩余电子的各种类型的重排。通常，这种重排会导致更多电子的延迟发射，这些延迟的大小最终决定了分子分解的方式和分解过程的时间尺度。因此，我计划投入相当大的努力，试图预测各种电子重排过程的时间尺度，并确定影响这些时间尺度的主要因素。所提出的理论工作的结果将指导新型X射线辐射源的应用，朝着用单分子X射线衍射测定分子结构的方向发展。

Understanding of mechanisms guiding the wide variety of biochemical processes in living organisms requires determination of structure of the biomolecules (for example, proteins) taking part in these processes. Indeed, vast scientific resources have been put into trying to unveil protein structure. The spectacular success that has been achieved along this path has contributed immensely to our ability to fight diseases by designing new drugs. Throughout the last century, this success has been marked by numerous Nobel Prizes in Physics and Chemistry. In spite of the remarkable achievements of the present-day methods, the structures of a vast bulk of biomolecules still remain a mystery. The reason is that the prerequisite for application of the main existing technique, called X-ray diffraction, is crystallization of the biomolecules under study. It turns out that obtaining a crystal, that is a geometrically ordered solid structure, out of protein solution is often an extremely difficult task. To overcome this difficulty, some researchers suggested to analyse proteins by X-ray diffraction in gas phase rather than in a crystal. This would certainly require application of much more intense X-ray radiation than the one available today since this way one would try to obtain a picture of a single biomolecule. Fortunately though, new powerful X-ray sources called X-ray free electron lasers are now being built at a number of facilities throughout the world. It has been proposed that the X-ray radiation generated by these new sources will be strong enough to give a picture of a single protein molecule in a single shot. The principal problem with such an approach is that the very same radiation that creates an image of a target molecule can also destroy the target. The fate of the new method of the single-molecule X-ray diffraction hangs on the delicate balance between these two basic consequences of X-ray-molecule interaction: diffraction of the radiation versus decomposition of the molecule. The central problem is to design such a radiation pulse that is strong enough and long enough to provide the diffraction picture of sufficient quality, but still short enough not to cause the molecule to disintegrate during the action of the pulse. Design of such pulses is possible only if one is able to understand in detail all possible mechanisms of molecular decomposition and eventually to model it in a computer simulation. The central goal of the present proposal is exactly this: theoretical study of the electronic processes that lead to disintegration of a molecule under the action of intense X-ray and computer simulation of this process based on the detailed understanding of the underlying physical mechanisms. These mechanisms include ionisation of molecules by the X-ray radiation and various types of rearrangements of the remaining electrons following the ionisation events. Often, such rearrangements lead to a delayed emission of more electrons and the magnitudes of these delays determine eventually the way in which the molecule decomposes and the time scale of the decomposition process. Thus, I plan to invest a considerable effort in trying to predict the time scales of the various electronic rearrangement processes as well as to determine the main factors that affect these time scales. The results of the proposed theoretical work will guide the application of the novel X-ray radiation sources towards towards determination of molecular structure by single-molecule X-ray diffraction.