Dr. Abagyan has previously demonstrated that an improved energy function, combined with a powerful conformational search procedure, can accurately predict the detailed (all-atom) structure of small molecules and polypeptide fragments. It is proposed to apply these advances to the development of a comprehensive and accurate homology prediction procedure. Application of this method to homology modeling test cases showed that it permits successful prediction of loops and side chains under idealized conditions. However, the deformed yet rigid structural environment of modeled loops or other backbone fragments was found to be the largest obstacle to successful homology modeling. It is proposed: to adapt the loop modeling method to permit rearrangements in the loop's surroundings; to automate the determination of this """"""""soft"""""""" environment; to apply the prediction method to polypeptide ends, mobile secondary structure elements and peptide plane orientation errors; to test and refine all components of the method, using an optimal test set of known homologous pairs from the standard database.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM055418-02
Application #
2771077
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1997-09-30
Project End
1999-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
New York University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10016
Fernandez-Recio, Juan; Totrov, Maxim; Abagyan, Ruben (2002) Soft protein-protein docking in internal coordinates. Protein Sci 11:280-91
Fernandez-Recio, Juan; Totrov, Maxim; Abagyan, Ruben (2002) Screened charge electrostatic model in protein-protein docking simulations. Pac Symp Biocomput :552-63
Cardozo, T; Batalov, S; Abagyan, R (2000) Estimating local backbone structural deviation in homology models. Comput Chem 24:13-31
Maiorov, V; Abagyan, R (1998) Energy strain in three-dimensional protein structures. Fold Des 3:259-69
Zhou, Y; Abagyan, R (1998) How and why phosphotyrosine-containing peptides bind to the SH2 and PTB domains. Fold Des 3:513-22