AHPCRC Projects
Project 2–4: Protein Structure Prediction for Virus Particles Principal Investigator: Enrico Pontelli (New Mexico State University) |
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| Protein structure fragments are assembled to make the model. | Protein structure models with varying levels of detail. | |
| Graphics this page courtesy Enrico Pontelli (New Mexico State University). | ||
Viruses, one major category of biological warfare agents, mutate rapidly and can be genetically engineered to resist existing vaccines. Protein structure prediction, a well-known tool for pharmaceutical development, can point to likely adaptations of known viruses and guide efforts to combat the new forms. This method is computationally intensive and requires advanced visualization tools to be effective—making this field an ideal candidate for high performance computing. AHPCRC researchers have developed a computational method to assemble fragments of a protein structure, an important step in predicting the structure of viruses. The protein fragments are identified using an existing protein databank (the PDB), considering both the protein sequence information and the geometrical constraints provided by laboratory analysis of virus particles. The results have proven this method to be faster and more accurate than a popular conventional loop modeling method. A computational mutation energy analysis method has been developed to study the topological mutations of secondary structure elements of a protein. This method, which has been adapted to run on parallel computing clusters, requires only partial structure information to evaluate the stability of a permutation. Comparison of energetically stable structures obtained using this method with structures observed in laboratory studies has shown that the method consistently ranks native topologies at or near the top of ranked lists of thousands of possible topologies. Intentionally engineered virus structures are one promising avenue of application for computational structure prediction research. Because viruses are naturally self-replicating nanoparticles, they have potential use as drug delivery devices. A thorough understanding of virus structures and their functions is vital to ensuring that such engineered viruses are safe and effective. |
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