Wolfgang Bitomsky and Rebecca C. Wade
European Molecular Biology Laboratory, 69012 Heidelberg, Germany
Abstract:
Heparin-protein interactions play an important role in many steps of the immune system. Here, we evaluated the search capabilities of three widely used programs-GRID, DOCK, and AutoDock-for heparin binding sites. Because of the weak surface complementarity and the high charge density of the sulfated sugar chain, the docking of heparin to its protein partners presents a challenging task for computational docking. Our protocols were tested on antithrombin and acidic and basic fibroblast growth factor, the only three proteins for which structures of their complexes with heparin are available. With all three programs, the heparin binding site for these test cases was determined correctly. We then used these protocols to predict the heparin binding site on Interleukin-8, a chemokine with a central role in the human immune response. The results indicate that His18, Lys20, Arg60, Lys64, and Arg68 in interleukin-8 bind to heparin.
J. Am. Chem. Soc. (1999) 121, 3004-3013.