CCPNGrid: A framework for high throughput computing in NMR spectroscopy

蛋白质是生物体的主力。它们参与了许多功能，没有它们，我们所知道的生命就不可能存在。例如，在人体中，某些蛋白质在血液中运输氧气，其他蛋白质保护我们免受细菌和病毒的侵害，还有一些蛋白质帮助消化食物。所有蛋白质都是由氨基酸组成的。这些氨基酸是蛋白质的组成部分，它们相互连接形成一条长链。天然存在的氨基酸有20种，每种都有不同的形状。由于每种蛋白质都有独特的氨基酸序列，因此蛋白质链在三维空间中的折叠方式也是独特的。例如，链的一部分可以折叠回自己（β发夹），或者它可以折叠成线圈状结构（α螺旋）。然后，这些结构元素的组合相互作用，形成蛋白质的完整折叠。为了理解蛋白质是如何工作的，我们需要知道这条氨基酸长链是如何折叠的。这可以用两种技术来确定：x射线晶体学和核磁共振（NMR）光谱学。这个建议是针对NMR的。通过核磁共振，你可以确定蛋白质中哪些原子在空间上彼此靠近。例如，如果蛋白质链形成一个圆圈，你可以确定第一个氨基酸的原子与最后一个氨基酸的原子在空间上是接近的，等等。核磁共振实验产生了大量这类距离信息，需要在计算机上进行漫长的计算才能确定蛋白质链的确切折叠。这些计算基本上将距离信息转换为三维坐标。这被称为“结构计算”，它可以用许多不同的方法来完成。此外，这些结构计算相当复杂，需要大量的专业知识才能在计算机上进行设置。我们建议在一套快速的计算机上自动设置和运行最新、最先进的结构计算软件。该软件将通过互联网提供给研究人员，这样他们就可以毫不费力地使用最先进的软件。如果他们有足够快的计算机，他们也可以把它安装在自己的实验室里。即使你使用最好的软件，结构计算的结果仍然有可能存在问题。这可能是由于在分析NMR数据时所犯的错误，或者仅仅是因为我们在开始计算时没有足够的信息来得到一个好的答案。出于这个原因，我们还将自动运行验证程序来分析计算产生的结构。这种验证将有助于研究人员发现结果是否在科学上正确。最后，我们可以使用计算设置来重新计算旧的结构。蛋白质数据库（PDB）存储了世界各地人们计算出的蛋白质结构。然而，不同的科学家计算这些结构的方法可能非常不同，而且很难直接将这些结构相互比较。使用相同的程序重新计算结构将提高结构的质量。它们也会更加一致，更容易直接进行比较。

Proteins are the workhorses of a living organism. They are involved in many functions, and without them life as we know it could not exist. In a human body for example, certain proteins transport oxygen in the blood, others defend us against bacteria and viruses, and still others help to digest food. All proteins are composed of amino acids. These amino acids are the building blocks of proteins, and they are connected to each other to form a long chain. There are 20 naturally occurring types of amino acid, each with a different shape. Because each protein has a unique amino acid sequence, how the protein chain folds in 3D space is also unique. For example, a part of the chain can fold back on itself (beta-hairpin), or it can fold into a coil-like structure (alpha-helix). A combination of these structural elements then interact with each other to form the complete fold of the protein. To understand how a protein works, we need to know how this long chain of amino acids folds. This can be determined using two techniques: X-ray crystallography and Nuclear Magnetic Resonance (NMR) spectroscopy. This proposal is directed at NMR. With NMR, you can determine which atoms in the protein are close to each other in space. For example, if the protein chain forms a circle, you can determine that the atoms of the first amino acid are close in space to the atoms of the last amino acid etc. NMR experiments produce a lot of this type of distance information, and a lengthy calculation on a computer is necessary to determine the exact fold of the protein chain. These calculations basically convert distance information into three-dimensional coordinates. This is called a 'structure calculation', and it can be done in many different ways. Also, these structure calculations are quite complex and require a lot of expertise to set up on a computer. We propose to set up and run automatically the latest and most sophisticated structure calculation software on a set of fast computers. This software would be available over the internet to researchers, so that they can use state-of-the-art software with little effort. They could also install it in their own laboratories if they have sufficiently fast computers of their own. Even if you are using the best software, it is still possible that there are problems with the results of the structure calculation. This can be due to mistakes made when analyzing the NMR data, or just because we did not have enough information to get a good answer when we started the calculation. For this reason, we will also automatically run validation programs that analyse the structures resulting from the calculation. This validation will help the researcher find out whether the results are scientifically correct. Finally, we can use the calculation setup to recalculate old structures. The Protein Data Bank (PDB) stores the structures of proteins that were calculated by people all over the world. The way different scientists calculate the structures can, however, be very different, and it can be difficult to directly compare the structures to each other. Recalculating the structures using the same program will improve the quality of the structures. They will also be more consistent with each other, and it will be easier to compare them directly.