Jobs with names DOCKING_*rhj* is running protein-protein docking on dimers where the individual monomers are related by symmetry. The structures are coming from ab-initio structure prediction. The structure of this protein could not be solved by standard techniques used for determining crystal structures. Although a crystal could be grown and experimental data looks good one of the procdures in crystal structure determination, phasing, could not succesfully be carried out starting from similar proteins previously solved. The idea here is to create models with ab-intio+docking that can be used as starting points for the phasing procedure. If this works this could be way of rescuing data from x-ray crystallography data from biologically important proteins that can not be converted to 3D-structures, which would a significant breakthrough.

Thanks for your help!

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We're running a new kind of workunit with the tag SYMM_FOLD_AND_DOCK in the names. These are some pretty crazy jobs -- you'll see two protein chains shaking and dancing around each other. We're trying to predict structures of proteins that form symmetric multimers (a category that includes many many proteins including virus coats and proteins that modulate DNA transcription). Previously you've seen straight folding of one chain, and docking of two structured chains, but this is the first time we're simultaneously exploring the fold and the relative orientation of the chains. This is a huge conformational space to explore, and is onl possible with Rosetta@home.

A first application of this new protocol is to a structural genomics target (s036) for the purpose of "phasing" crystallographic data -- see the post by Ingemar below.

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In the previous post Rhiju described a simulation called FOLD-AND_DOCK where we are predicting the structure of protein complexes from sequence alone. In a cell few proteins carry out their function on their own. Most proteins are either forming complexes with other proteins a fraction of the time (and the structure of these is something we try to predict with protein-protein docking simulations) or form permanent complexes consisting of multiple chains. Predicting the structure of a protein complex from sequence(s) of the involved chains is something that has never been shown, mostly because of the enormous search space that has to be covered in such a simulation.

A very important class of protein complexes are those that contains multiple copies of the same type of chain, we call them homooligomeric. A vast majority of these homooligomeric proteins contains some type of internal symmetry. For example, the most abundant form of homooligomers are dimers (two identical chains) and most are symmetrical: if you rotate one chain 180 degrees you get the other partner in the complex.

The fact that they are symmetrical allow us to reduce the search problem (all the chain are internally identical and are related by a set of rotations and translations specified by the type of symmetry). This makes it feasible to try to predict the structure of symmetrical protein complexes from sequence. Its still a huge search problem, and thats why we need your help!

Right now we are trying to predict the structure of a protein with pdb code 1zpy. The size of this protein is actually around 900 residues and if we succeed it would make the largest protein structure predicted to atomic accuracy from sequence (About 8 times larger than anything predicted before). We
are not actually simulating the whole protein, we can make use of symmetry to reduce the problem, but its still a large simulation. So if you get a job with the 1zpy in the name be patient!

Why are we doing this? Homooligomeric proteins are a biologically very important class of proteins. They are forming virus capsids, proteins that cleaves DNA, hemoglobin that transport oxygen, actin involved in muscle contraction, channels that transport ions and secretion systems used by pathogenic bacteria just to give a few examples.

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