Rosetta@home

What is Rosetta@home?

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Blind Protein Structure Prediction High-Resolution Protein Structure Prediction Protein Design Protein-Protein Docking
  • What is Rosetta@home?
  • Why predict and design protein structures and complexes?
  • How accurate are our predictions?
  • Plans for the future
  • Feedback to participants
  • View Windows Media videos of Rosetta predictions

    What is Rosetta@home?

    Rosetta@home needs your help to determine the 3-dimensional shapes of proteins in research that may ultimately lead to finding cures for some major human diseases. By running the Rosetta program on your computer while you don't need it you will help us speed up and extend our research in ways we couldn't possibly attempt without your help. You will also be helping our efforts at designing new proteins to fight diseases such as HIV, Malaria, Cancer, and Alzheimer's (See our Disease Related Research for more information). Please join us in our efforts! Rosetta@home is not for profit.
    Follow us on Twitter: @rosettaathome        

    We believe that we are getting closer to accurately predicting and designing protein structures and protein complexes, one of the holy grails of computational biology. But in order to prove this, we require an enormous amount of computing resources, an amount greater than the world's largest super computers. This is only achievable through a collective effort from volunteers like you.

    For more information, click on the following links:

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    Why predict and design protein structures and complexes?

    Proteins are the molecular machines and building blocks of life. Their functions and interactions are critical for the chemical and biological framework and processes of all living organisms. The function of a protein and how it iteracts with other molecules are largely determined by its shape (the three-dimensional structure). Proteins are initially synthesized as long chains of amino acids and, for the most part, they cannot function properly until they fold into intricate globular structures. Understanding and predicting the rules that govern this complex folding process -- involving the folding of the main backbone and the packing of the molecular side chains of the amino acids -- is one of the central problems of biology. Knowing how proteins fold and interact with other molecules and determining their functions may ultimately lead to drug discoveries and cures for human diseases. Currently, millions of dollars are being spent in structural genomics efforts to determine the structures of proteins experimentally using X-ray crystallography and nuclear magnetic resonance (NMR). If this could be done computationally, it would significantly reduce the cost and revolutionize structural biology. Designing protein structures and complexes also offers significant scientific and practical benefits. If one can design completely new structures, one can potentially design novel molecular machines -- proteins for carrying out new functions as therapeutics, catalysts, etc. And finally, there's the evolutionary question of whether the folds that are sampled in nature are the limit to what's possible; or whether there are quite different folds that are also possible. Understanding the rules that govern folding and design may help answer this question.

    Please visit the following Wikipedia links for more general information about:

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    How accurate are our predictions?

    CASP6 Target T281 Rosetta was shown repeatedly to be one of the best methods for predicting the three-dimensional structures of proteins in the Critical Assessment of Techniques for Protein Structure Prediction (CASP), and has also been successful in CAPRI, the Critical Assessment of Prediction of Interactions. A highlight of CASP6 was the first de novo blind prediction that used our high-resolution refinement methodology to achieve close to high-resolution accuracy. The relatively short sequence (76 residues) allowed us to apply our all-atom refinement methodology not only to the native sequence but also to the sequence of many homologs. The center of the lowest energy cluster of structures turned out to be remarkably close to the native structure (1.5 Å). The-high resolution refinement protocol decreased the RMSD from 2.2 Å to 1.5 Å, and the side chains pack in a somewhat native-like manner in the protein core. In CAPRI, predictors are given the structures of two proteins known to form a complex, and challenged to predict the structure of the complex. Our predictions for targets without significant backbone conformational changes were striking. Not only were the rigid-body orientations of the two partners predicted nearly perfectly but also almost all the interface side chains were modeled very accurately. Our design methods also have shown to produce accurate results. Particularly exciting recently is the creation of novel proteins with arbitrarily chosen three-dimensional structures. For example, our methods were used to design a 93-residue protein called TOP7 with a novel sequence and topology. TOP7 was found to be monomeric and folded, and the x-ray crystal structure of TOP7 is strikingly similar (RMSD of 1.2 Å) to the design model.

    Plans for the future

    Our methods will be tested in upcoming CASP and CAPRI experiments and implemented in our publicly available protein structure prediction server, Robetta, which is currently used by hundreds of academic scientists from around the world for free, and has been shown to be one of the best fully-automated structure prediction servers in recent CASP experiments. If there are enough Rosetta@home participants, we also plan to use Rosetta@home to provide computational resources that will reduce the long wait period for structure predictions on the Robetta server and will enable us to add more functionality, such as design and docking, that we currently cannot provide because of limited computing resources. By integrating Robetta and Rosetta@home, volunteers, like you, will not only help our efforts, but will directly help the efforts of scientists from around the world doing critical research on biomedical issues such as cancer, SARS, HIV/AIDS, malaria, and much more.

    Feedback to participants

    Wouldn't you, as a participant, like to know the results of the predictions made on your computer -- how accurate your best model was, how did it compare with others, what did it look like, who and how has it helped? We plan to provide such information on the Rosetta@home website and, when possible, link it to the predictions requested by scientists through the Robetta server. You can already keep track of the amount of computing work ("credits") that you have donated and compare it to others from our statistics page.
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    View Windows Media videos of Rosetta predictions


    Note: Windows Media Player is required. Videos were created by Jens Meiler.
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    Last Modified: 8 Apr 2009 22:29:18 UTC
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