RECONSTRUCTING PROTEINS FROM CHEMICAL SHIFT INFORMATION

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Reconstructing a protein in three-dimensions from its backbone torsion angles is an ongoing challenge because minor inaccuracies in these angles produce major errors in the structure. Against this background, we are conducting a computational experiment to assess whether protein conformation can be determined from highly approximate backbone torsion angles, the kind of information that is now obtained readily from NMR. Specifically, backbone torsion angles are taken from proteins of known structure and mapped into 60 x 60 grid squares, called mesostates. Sidechain atoms beyond the ?-carbon are discarded. A mesostate representation of the protein backbone is then used to extract likely candidates from a fragment library of mesostate pentamers, followed by Monte Carlo-based fragment-assembly simulations to identify stable conformations compatible with the given mesostate sequence. Only three simple energy terms were used to gauge stability: molecular compaction, soft-sphere repulsion, and hydrogen-bonding. Initial results have been published in: 1. Haipeng Gong, Patrick J. Fleming and George D. Rose (2005) Building native protein conformation from highly approximate backbone torsion angles. Proc Nat. Acad. Sci., 102: 16227-16232. 2. Patrick J. Fleming, Haipeng Gong, and George D. Rose (2006) Secondary structure determines protein topology. Protein Science (accelerated publication), in press. We are now ready to put these ideas to the test by doing many simulations for a larger representative selection of proteins.