Showing papers on "Docking (molecular) published in 1988"

Using shape complementarity as an initial screen in designing ligands for a receptor binding site of known three-dimensional structure

Abstract: Finding novel leads from which to design drug molecules has traditionally been a matter of screening and serendipity. We present a method for finding a wide assortment of chemical structures that are complementary to the shape of a macromoleculer receptor site whose X-ray crystallographic structure is known. Each of a set of small molecules from the Cambridge Crystallographic Database (Allen; et al. J. Chem. Doc. 1973, 13, 119) is individually docked to the receptor in a number of geometrically permissible orientations with use of the docking algorithm developed by Kuntz et al. (J. Mol. Biol. 1982, 161, 269). The orientations are evaluated for goodness-of-fit, and the best are kept for further examination using the molecular mechanics program AMBER (Weiner; Kollman J. Comput. Chem. 1981, 106, 765). The shape-search algorithm finds known ligands as well as novel molecules that fit the binding site being studied. The highest scoring orientations of known ligands resemble binding modes generated by interactive modeling or determined crystallographically. We describe the application of this procedure to the binding sites of papain and carbonic anhydrase. While the compounds recovered from the Cambridge Crystallographic Database are not, themselves, likely to be inhibitors or substrates of these enzymes, we expect that the structures from such searches will be useful in the design of active compounds.

Electrostatics and molecular recognition

Abstract: This short communication outlines preliminary work aimed at understanding the recognition of sialylated oligosaccharides by influenza virus haemagglutinin. Initial efforts to model the complex have used the electrostatic interactions between atoms in the binding pocket and (2) as a means of constraining the conformational search in docking these two molecules. Some important features of the lowest energy structure are discussed.