We have been docking small molecules (e.g., drugs) into proteins using Monte Carlo (MC) simulation. The binding of a flavonoid inhibitor to cyclin dependent kinase 2 serves as a model system to investigate the reliability of computer simulations that allow both the protein and ligand to be flexible. In the absence of a crystal structure of the complex, such flexibility must be reliably handled to optimize drugs for proteins. In addition, a variety of programs were applied to docking problems to identify strengths and weaknesses of different software packages.Molecular modeling was used to assess the structural requirements for catalysis and dimerization of human methionine adenosyltransferase I/III. A manuscript was submitted for publication.Molecular modeling was also used to compare the amino acid presentation in the combining site between two anti-yeast iso-1 cytochrome c monoclonal antibodies whose epitopes are closely related. A manuscript was submitted for publication.The tetrameric state of the short coiled coil domain of the ORFIII product of cauliflower mosaic virus has been determined by several experimental methods. The 3D structure of the coiled coil tetramer was modeled in order to understand the structural principles of the alpha-helical coiled coil oligomerization. Several amino acid mutations were introduced into the coiled coil fragment based on the analysis of the modeled structure. The mutant structures were experimentally analyzed. A manuscript was submitted for publication.

Agency
National Institute of Health (NIH)
Institute
Center for Information Technology (CIT)
Type
Intramural Research (Z01)
Project #
1Z01CT000259-03
Application #
6103842
Study Section
Special Emphasis Panel (CMM)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Center for Information Technology
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Henry, L Keith; Field, Julie R; Adkins, Erika M et al. (2006) Tyr-95 and Ile-172 in transmembrane segments 1 and 3 of human serotonin transporters interact to establish high affinity recognition of antidepressants. J Biol Chem 281:2012-23
Kajava, Andrey V; Kobe, Bostjan (2002) Assessment of the ability to model proteins with leucine-rich repeats in light of the latest structural information. Protein Sci 11:1082-90
Kalinin, Andrey E; Kajava, Andrey V; Steinert, Peter M (2002) Epithelial barrier function: assembly and structural features of the cornified cell envelope. Bioessays 24:789-800
Terskikh, Alexey V; Fradkov, Arkady F; Zaraisky, Andrey G et al. (2002) Analysis of DsRed Mutants. Space around the fluorophore accelerates fluorescence development. J Biol Chem 277:7633-6
Kajava, A V; Cheng, N; Cleaver, R et al. (2001) Beta-helix model for the filamentous haemagglutinin adhesin of Bordetella pertussis and related bacterial secretory proteins. Mol Microbiol 42:279-92
Kobe, B; Kajava, A V (2001) The leucine-rich repeat as a protein recognition motif. Curr Opin Struct Biol 11:725-32
Kajava, A V (2001) Review: proteins with repeated sequence--structural prediction and modeling. J Struct Biol 134:132-44
Potekhin, S A; Melnik, T N; Popov, V et al. (2001) De novo design of fibrils made of short alpha-helical coiled coil peptides. Chem Biol 8:1025-32
Spirina, O; Bykhovskaya, Y; Kajava, A V et al. (2000) Heart-specific splice-variant of a human mitochondrial ribosomal protein (mRNA processing; tissue specific splicing). Gene 261:229-34
Kajava, A V (2000) alpha-Helical solenoid model for the human involucrin. FEBS Lett 473:127-31

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