Applied and Interdisciplinary Mathematics Seminar

University of Michigan

Fall 2007
Wednesday, 31 October, 4:10-5:00pm, Great Lakes South, Palmer Commons Building, Fourth Floor

The Modulation of Hydrophobicity in Protein-Ligand Interactions

L. Ridgway Scott

The University of Chicago


Abstract

The digital nature of biology is crucial to its functioning as an information system, as well in building hierarchical components. We attempt to explain how protein systems can function as discrete components, despite the importance of non-specific forces due to the hydrophobic effect. We address the question of why proteins bind to other proteins predictably and not in a continuous distribution of places, the way grease forms into blobs. We explain how the differences in hydrophobicity in sidechains cause the modulation of the dielectric effect in the vicinity of proteins. This in turn has a significant effect on the strength and stability of certain electrostatic bonds, which in turn guide the interaction of proteins and ligands. We will give a detailed description of how data mining in the PDB can give clues to how proteins interact. This work makes precise the notion of hydrophobic interaction in certain cases. It provides an understanding of how molecular recognition and signaling can evolve. This work also introduces a new model of electrostatics for protein-solvent systems that presents significant computational challenges. We give an example of the use of our ideas in drug design.