The Molecular Modeling Section uses and develops theoretical tools to study and predict the structure and stability of globular protein molecules and to design protein molecules with new or improved properties. Following are some of the research activities and results that we obtained during this reporting period: (1) The in-house molecular graphics program, GEMM, is being modified in order to use the open GL graphics library. This modification will make the program run faster on modern workstations. (2) A new protein structure prediction method was devised that uses a discrete set of states and a hierarchical search procedure. The work is only at the beginning stage, but preliminary results are highly encouraging. (3) A new fast procedure was developed for making protein structure comparisons. Because the procedure is fast, we could compare all known protein structures with all others and cluster them into structurally homologous protein groups. The results are being analyzed currently. (4) In collaboration with the Molecular Biology Section, we (a) designed mutations to increase the stability and binding properties of a number of tumor-specific antibodies, (b) designed mutations to reduce the liver toxicity of an immunotoxin, (c) designed a new single-chain Fv molecule by base loop exchange and sequence permutation, and (d) designed peptide linkers for an MHC molecule and a peptide from gp100 so that the ternary complex can be expressed as a single-chain molecule. (5) By analyzing the expressed sequence tag (EST) database, we identified three previously uncharacterized genes specifically expressed in the human prostate but not in other organs. We are working to identify other such genes, and in collaboration with the Molecular Biology Section, characterizing the genes and the gene products.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC008759-07
Application #
6100931
Study Section
Special Emphasis Panel (LMB)
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1998
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Das, Sudipto; Hahn, Yoonsoo; Walker, Dawn A et al. (2008) Topology of NGEP, a prostate-specific cell:cell junction protein widely expressed in many cancers of different grade level. Cancer Res 68:6306-12
Hahn, Yoonsoo; Jeong, Sangkyun; Lee, Byungkook (2007) Inactivation of MOXD2 and S100A15A by exon deletion during human evolution. Mol Biol Evol 24:2203-12
Das, Sudipto; Hahn, Yoonsoo; Nagata, Satoshi et al. (2007) NGEP, a prostate-specific plasma membrane protein that promotes the association of LNCaP cells. Cancer Res 67:1594-601
Grigoryev, Dmitry N; Ma, Shwu-Fan; Shimoda, Larissa A et al. (2007) Exon-based mapping of microarray probes: recovering differential gene expression signal in underpowered hypoxia experiment. Mol Cell Probes 21:134-9
Bera, Tapan K; Saint Fleur, Ashley; Lee, Yoomi et al. (2006) POTE paralogs are induced and differentially expressed in many cancers. Cancer Res 66:52-6
Hahn, Yoonsoo; Lee, Byungkook (2006) Human-specific nonsense mutations identified by genome sequence comparisons. Hum Genet 119:169-78
Sam, Vichetra; Tai, Chin-Hsien; Garnier, Jean et al. (2006) ROC and confusion analysis of structure comparison methods identify the main causes of divergence from manual protein classification. BMC Bioinformatics 7:206
Hahn, Yoonsoo; Bera, Tapan K; Pastan, Ira H et al. (2006) Duplication and extensive remodeling shaped POTE family genes encoding proteins containing ankyrin repeat and coiled coil domains. Gene 366:238-45
Egland, Kristi A; Liu, Xiu Fen; Squires, Stephen et al. (2006) High expression of a cytokeratin-associated protein in many cancers. Proc Natl Acad Sci U S A 103:5929-34
Hahn, Yoonsoo; Lee, Byungkook (2005) Identification of nine human-specific frameshift mutations by comparative analysis of the human and the chimpanzee genome sequences. Bioinformatics 21 Suppl 1:i186-94

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