Hydrophobic and electrostatic driving forces for protein-membrane docking: A combined experimental and computational approach
Studying how proteins inside a cell interact with the cell’s membrane, or outer “skin,” is one very important key to understanding protein function. By localizing to a particular cell membrane, proteins affect how the cell functions, or in the cases of disease such as cystic fibrosis, malfunctions. Jefferson Knight and Hai Lin, two chemists from the University of Denver, are attempting to understand the subtle differences in how two similar proteins “dock,” or attach themselves to cell membranes. The proteins under investigation are called “synaptotagmins,” based on their functions in synapses, the communication junctions between brain cells. One of the proteins employs an “electrostatic” docking method, which, as the name implies, involves forces of natural electrical charge; but the term also generally includes the somewhat more mysterious, and very weak, van der Waals force, which is the sum of the extremely subtle attractive or repulsive forces occurring between molecules. The other protein, although similar in structure, employs a method of cell docking called hydrophobic (“water-fearing”) interaction. The term describes the;segregation and apparent repulsion between water and “nonpolar” substances – basically molecules whose electrons are distributed symmetrically, so that they don’t have strong positive and negative charges.The most widely known result is oil’s reluctance to mix with water. (Water is a “polar” molecule, meaning that there is an uneven distribution of electron density.) With their RCSA grant Knight and Lin and their students will perform experiments to identify the key amino acid residues contributing to electrostatic and hydrophobic interactions. Using modeling techniques, they will measure and compare the structures of the two protein molecules, and then they will employ computer simulations to, theoretically at least, alter the molecules’ shapes to see how these changes affect their docking preferences. The researchers said they hope their work will lead to better membrane-targeted drugs. (Roughly 50 percent of all modern medicinal drugs are targeted to the proteins composing our cells’ membranes).