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 #
5R01GM046535-08
Application #
6179373
Study Section
Allergy and Immunology Study Section (ALY)
Program Officer
Wehrle, Janna P
Project Start
1992-05-01
Project End
2000-08-31
Budget Start
2000-04-01
Budget End
2000-08-31
Support Year
8
Fiscal Year
2000
Total Cost
$7,057
Indirect Cost
Name
Texas A&M University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
078592789
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
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
Linthicum, D S; Tetin, S Y; Anchin, J M et al. (2001) Antibody-ligand interactions: computational modeling and correlation with biophysical measurements. Comb Chem High Throughput Screen 4:439-49
Gibas, C J; Jambeck, P; Subramaniam, S (2000) Continuum electrostatic methods applied to pH-dependent properties of antibody-antigen association. Methods 20:292-309
Rojnuckarin, A; Livesay, D R; Subramaniam, S (2000) Bimolecular reaction simulation using Weighted Ensemble Brownian dynamics and the University of Houston Brownian Dynamics program. Biophys J 79:686-93
Viswanathan, M; Linthicum, D S; Subramaniam, S (2000) Analysis of correlated motion in antibody combining sites from molecular dynamics simulations. Methods 20:362-71

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