QUANTUM CRYSTALLOGRAPHY OF BIOLOGICAL MOLECULES--INSULIN AND ITS FRAGMENTS

这项研究的长远目标是发展下一代晶体学，即直接建立在量子力学基础上的晶体学，并适用于蛋白质和DNA。我们的具体目标是生物学上重要的蛋白质胰岛素的量子晶体学。这项研究的影响，包括首次获得胰岛素分子的量子几何和电子结构，而且还提供了一种普遍适用于蛋白质和DNA以及与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。量子晶体学提供了几何结构和电子结构，前者是“锁与钥匙”分子相互作用可能性的决定因素，后者决定了这种相互作用的强度和机制。这对于合理的药物设计是非常重要的。我们的研究设计是基于量子力学的认识，原子轨道重叠随着原子间距离的增加而迅速减少。轨道的这种“近视性”导致了对整个生物分子的描述，即其各部分的总和，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，蛋白质和DNA等大分子的量子力学被严格地简化为对它们片段的认识，极大地简化了它们晶体结构的实验和理论组成部分。碎片概念同样适用于晶体x射线结构的细化及其从薛定谔方程的从头计算。两种情况的比较保证了结果的准确性。在这两种情况下，所涉及的时间基本上随复杂性线性增加，从而使生物分子的量子特性切实可行。

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.