Recent years'CASP experiments have seen significant progress on computer-based protein tertiary structure prediction. The state-of-the-art algorithms, such as TASSER, can generate correct folds for 2/3 of single domain proteins without using homologous templates. Most of the models are of low resolution with a root mean square deviation (RMSD) 3-6 Angstroms, which may be useful for protein topology analysis and some level of biological function inference. However, such models are not suitable for reliable ligand screening. The proposed research seeks to develop new methodologies for the atomic-level high-resolution protein structure modeling.
The specific aims are: (1) development of a new algorithm, atom-TASSER, for atomic-level protein structure modeling;(2) development of a two-level composite potential for both the low-resolution topology construction and the high-resolution refinement;(3) force field optimization in both structure and sequence phase spaces;(4) large-scale benchmarking of atom-TASSER algorithm. Overall, these studies are designed to extend the range of validity of the reduced modeling approaches, and provide significant improvements in the state-of-the-art of tertiary structure prediction. The goal is to push up the level of accuracy of computer-based modeling, especially for the distant/weakly homologous proteins, so that they can be of real use to new drug screening and biochemical functional inference.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM083107-06
Application #
8247020
Study Section
Macromolecular Structure and Function D Study Section (MSFD)
Program Officer
Wehrle, Janna P
Project Start
2008-04-01
Project End
2013-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
6
Fiscal Year
2012
Total Cost
$255,909
Indirect Cost
$90,272
Name
University of Michigan Ann Arbor
Department
Biostatistics & Other Math Sci
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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