Human Proteome Folding - Phase 2

Project Status and Findings:   For the latest status report, please go to the Human Proteome Folding – Phase 2 status report. To comment or ask questions about this project, please submit a post in the Human Proteome Folding – Phase 2 Forum.

Human Proteome Folding Phase 2 (HPF2) continues where the first phase left off. The two main objectives of the project are to: 1) obtain higher resolution structures for specific human proteins and pathogen proteins and 2) further explore the limits of protein structure prediction by further developing Rosetta software structure prediction. Thus, the project will address two very important parallel imperatives, one biological and one biophysical.

The project, which began at the Institute for Systems Biology and now continues at New York University's Department of Biology and Computer Science, will refine, using the Rosetta software in a mode that accounts for greater atomic detail, the structures resulting from the first phase of the project. The goal of the first phase was to understand protein function. The goal of the second phase is to increase the resolution of the predictions for a select subset of human proteins. Better resolution is important for a number of applications, including but not limited to virtual screening of drug targets with docking procedures and protein design. By running a handful of well-studied proteins on World Community Grid (like proteins from yeast), the second phase also will serve to improve the understanding of the physics of protein structure and advance the state-of-the-art in protein structure prediction. This also will help the Rosetta developers community to further develop the software and the reliability of its predictions.

HPF2 will focus on human-secreted proteins (proteins in the blood and the spaces between cells). These proteins can be important for signaling between cells and are often key markers for diagnosis. These proteins have even ended up being useful as drugs (when synthesized and given by doctors to people lacking the proteins). Examples of human secreted proteins turned into therapeutics are insulin and the human growth hormone. Understanding the function of human secreted proteins may help researchers discover the function of proteins of unknown function in the blood and other interstitial fluids.

The project also will focus on key secreted pathogenic proteins. While still in its early design phases, HPF2 will likely focus on Plasmodium, the pathogenic agent that causes malaria. Researchers hope that higher resolution structure predictions for the proteins that malaria secretes will serve as bioinformatics infrastructure for researchers who are working hard around the world to understand the complex interaction between human hosts and malaria parasites. While there are few silver bullets, and biology is one of the most complicated subjects on earth, researchers believe that this work will help it understand elements of this host-pathogen interaction or at least its components. Researchers will provide their findings as a resource to the scientific community and then work with the community on visualizing, using and refining the data. This understanding could then be a foundation for intervention.

Lastly, this project dovetails with efforts at NYU and ISB to support predictive, preventative and personalized medicine (under the assumption that these secreted proteins will be key elements of this medicine of the future). It is too early to say which proteins will end up being biomarkers (substances sometimes found in an increased amount in the blood, other body fluids, or tissues and which can be used to indicate the presence of some types of cancer). However, it is clear that many will end up being secreted proteins. As in the first phase of the project, the power of World Community Grid will be critical in getting results quickly to researchers in the biological and biomedical communities.

For more information about proteome folding, click here.