The overall objective is to understand the chemical specificity of various biological receptor systems and their interactions with small bioactive ligands. This research project seeks to gain a preliminary insight into the physiochemical and macromolecular rules governing specific recognition and binding of bioactive ligands using modern molecular biology, biophysical measurements and supramolecular computational chemistry. The objective will be accomplished using theoretical and experimental molecular modelling studies in which we will use antibody-ligand binding sites as an exemplar of receptor-ligand interactions. Mimicry of biological receptor sites, in terms of their stereospecific recognition and binding of ligands, can serve as a model for the study of interactive and energetic constituents of both the ligand and receptor. We will use quantitative structure-activity ligand binding techniques, fluorescence spectroscopy techniques, gene sequencing and site-directed mutagenesis procedures, computer-aided modelling and dynamics simulations, and x-ray crystallography. This study is the first of its kind to use both theoretical and experimental approaches to characterize receptor binding sites for bioactive ligands. It is imperative that we understand the basis of receptor-ligand interactions so that strategies in designing new bioactive ligands and receptors may be developed in a rational and predictive manner.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM046535-07
Application #
2900760
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1992-05-01
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Texas A&M University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
047006379
City
College Station
State
TX
Country
United States
Zip Code
77845
Livesay, Dennis R; Subramaniam, Shankar (2004) Conserved sequence and structure association motifs in antibody-protein and antibody-hapten complexes. Protein Eng Des Sel 17:463-72
Livesay, Dennis R; Jambeck, Per; Rojnuckarin, Atipat et al. (2003) Conservation of electrostatic properties within enzyme families and superfamilies. Biochemistry 42:3464-73
Khare, Sangeeta; Banai, Yona; Gokulan, Kuppan et al. (2003) Early changes in metabolism of leukemic cell lines upon induction of apoptosis by cytotoxic drugs. Eur J Pharmacol 465:23-30
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Linthicum, D S; Patel, J; Cairns, N (2001) Antibody-based fluorescence polarization assay to screen combinatorial libraries for sweet taste compounds. Comb Chem High Throughput Screen 4:431-8
Khare, S; Gokulan, K; Linthicum, D S (2001) Cellular responses of NG108-15 and SK-N-MC lines to sweet and bitter tastants as measured by extracellular acidification rates. J Neurosci Res 63:64-71
Linthicum, D S (2001) Ultrastructural effects of silicic acid on primary lung fibroblasts in tissue culture. Tissue Cell 33:514-23
Herrgard, S; Gibas, C J; Subramaniam, S (2000) Role of an electrostatic network of residues in the enzymatic action of the Rhizomucor miehei lipase family. Biochemistry 39:2921-30
Khare, S; Gokulan, K; Linthicum, D S (2000) Vasoactive amine responses in murine cerebrovascular endothelial cells as measured by extracellular acidification rates. J Neurosci Res 60:356-61
Chen, J; Pattarawarapan, M; Zhang, A J et al. (2000) Solution- and solid-phase syntheses of substituted guanidinocarboxylic acids. J Comb Chem 2:276-81

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