MOLECULAR MODELING OF PROTEIN-LIGAND INTERACTIONS

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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.