QUANTUM CRYSTALLOGRAPHY OF BIOLOGICAL MOLECULES--INSULIN AND ITS FRAGMENTS

这项研究的广泛和长期目标是发展下一代结晶学，即直接建立在量子力学基础上的适用于蛋白质和DNA的结晶学。我们的具体目标是对具有生物重要性的蛋白质胰岛素进行量子结晶学研究。这方面的影响包括首次获得胰岛素分子的量子几何和电子结构，但也包括一种普遍适用于蛋白质和DNA以及它们相互作用的药物分子的方法。这些信息通过应用直接影响生物化学对健康的影响，这些应用遵循分子结构和功能的知识。量子晶体既提供了几何结构，这是决定分子相互作用可能性的决定因素，也提供了决定这种相互作用的强度和机制的电子结构。这对合理的药物设计的重要性将是巨大的。我们的研究设计是基于量子力学的实现，即原子轨道重叠随着原子间距离的增加而迅速减小。轨道的这种“近视性”导致了对整个生物分子的描述，用它的各部分之和来描述，称为核。量子描述只需要核和它们附近的几个原子，统称为碎片。因此，大分子的量子力学，例如蛋白质和DNA，被严格地简化为关于它们片段的知识，极大地简化了它们晶体结构的实验和理论成分。碎片概念同样适用于晶体结构的X射线精修及其薛定谔方程的从头计算。两个案例的比较确保了结果的准确性。在任何一种情况下，所涉及的时间基本上都随着复杂性的增加而线性增加，从而使得生物分子的量子特性实际上是可以获得的。

The broad, long term objectives of this research are to develop the next generation of crystallography, viz., one founded directly upon quantum mechanics, and applicable to proteins and DNA. Our specific aim is the quantum crystallography of the biologically important protein insulin. The impact of this, includes having for the first time the quantum geometrical and electronic structure of the insulin molecule, but also a methodology that will be generally applicable to proteins and DNA, and the drug molecules with which they interact. Such information impacts directly upon health implications of biochemistry through applications, which follow upon knowledge of molecular structure & function. Quantum Crystallography delivers both geometrical structure, the determining factor which underlies the possibility of :lock & key" molecular interactions, and electronic structure which determines the strength and mechanisms of such interactions. The importance of this for rational drug design would be enormous. Our research design is based upon the quantum mechanical realization that atomic orbital overlap decreases rapidly with interatomic distance. This "near-sightedness" of orbitals leads to a description of a whole biological molecule in terms of the sum of its parts, called kernels. The quantum description requires only the kernels and a few atoms in their neighborhood altogether called fragments. Thus, quantum mechanics of giant molecules, e.g., proteins and DNA, is rigorously reduced to knowledge of their fragments, vastly simplifying both experimental and theoretical components of their crystal structure. The fragment concept applies equally to the crystallographic X-ray refinement of structure and its ab initio calculation from the Schrodinger equation. Comparison of the two cases ensures accuracy of results. In either cases the time involved increases essentially linearly with complexity, thus making the quantum properties of biological molecules practicably attainable.