CCPNGrid: A framework for high throughput computing in NMR spectroscopy

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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.