DEVELOPMENT AND APPLICATION OF A HIERARCHICAL PROTOCOL FOR AB INITIO PREDICTION

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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Most of current research in computational biology an bioinformatics is focused on predicting the three-dimensional structure of proteins. Using different approaches, researches are trying to develop methodology for predicting proteins structure based only on amino acid sequence. However, three-dimensional structure alone is not sufficient to understand many biological processes which involve proteins. Research presented in this proposal is based on parameterization of our physics-based coarse-grained force-filed UNRES using information not only about the three dimensional structure of the native state of proteins but also about their folding mechanism and thermodynamic stability. We expect that such parameterization and extensive conformational space search using molecular dynamics enable us to simultaneously predict two protein properties: structure and thermodynamic stability of the native state and folding pathway(s) which lead from the unfolded to the folded state.