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Protein-protein and protein-substrate specificity
Protein-Protein and Protein-Substrate Specificity in Two Unique Membrane Bound Proteins
This researcher is working on the characterization of protein-protein and protein-substrate recognition/specificity by sweet taste receptors and organic anion transporting polypeptides (Oatps), respectively. In each case, the protein structures have been constructed by homology modeling for use in structure based hypothesis generation. Of interest for the sweet taste receptor is the extracellular hydrophilic domain and its interaction with both small ligands and, more importantly, with the sweet-tasting protein brazzein. Protein-protein docking and molecular dynamics are used to understand how brazzein binds and elicits its sweet taste, with interest in surface complimentarity and backbone flexibility. The computational work is being used to drive mutagenesis studies on brazzein. The Oatp project is concerned with small molecule transport selectivity across the cell membrane. Oatps appear to be members of the large Major Facilitator Superfamily (MFS) of transporters which this researcher has used for modeling. This project uses small molecule docking and dynamics, pharmacophore modeling, and 3D-QSAR.
The Oatp project is concerned with small-molecule transport selectivity across the cell membrane. Oatps appear to be members of the large Major Facilitator Superfamily (MFS) of transporters, three of which have known three-dimensional structures. All three structures have been used to generate a homology model of Oatp member 1c1, which is being used to guide mutagenesis studies. In addition, the researcher is using small molecule docking and dynamics, pharmacophore modeling, and 3D-QSAR to understand and predict substrate selectivity for transport across various tissue types. The MSI tools/software used for these studies include homology modeling, molecular dynamics, sequence analysis, pharmacophore modeling, comparative molecular field analysis (CoMFA), and DFT and semi-empirical small molecule modeling.