University of Minnesota
University Relations
http://www.umn.edu/urelate
612-624-6868

Minnesota Supercomputing Institute


Log out of MyMSI
RumbleyJN

Research Abstracts Online
January - December 2011

Main TOC ...... Next Abstract

University of Minnesota Duluth
College of Pharmacy Duluth
Department of Pharmacy Practice and Pharmaceutical Sciences

PI: Jon N. Rumbley

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, 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.