Molecular Docking In Molecular Docking

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Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. The goal of ligand—protein docking is to predict the predominant binding mode(s) of a ligand with a protein of known three-dimensional structure. Successful docking methods search high-dimensional spaces effectively and use a scoring function that correctly ranks candidate dockings. Garrett M. Morris and Marguerita Lim-Wilby, Molecular Docking, In Molecular Modeling of Proteins Methods in Molecular Biology, 2008, Volume 443 Virtual screening of compound libraries has become a standard technology in modern drug discovery pipelines [1]. If a suitable structure of the target is available molecular docking can be used to discriminate between putative binders and non-binders in large databases of chemicals and to reduce the number of compounds to be subjected to experimental testing substantially. Visual examination of predicted binding geometries (docking poses) thereby contributes crucially to the further development of a lead compound either towards enhanced binding affinity, towards reduced side effects or towards reduced susceptibility to drug resistance related mutations. Docking can be used to perform virtual screening on large libraries of compounds, rank the results, and propose structural hypotheses of how the ligands inhibit the target, which is invaluable in lead optimization. 2.6.1Introduction to molecular docking 2.6.1.1 Biological background Molecular docking is used to predict the structure of the intermolecular complex formed between two or more molecules. The most interesting case is the protein-ligand interaction, because of its applications in medicine. Ligand is a small molecule, which interacts with protein’s bind... ... middle of paper ... ...scoring functions and a large set of protein-ligand complexes with known protein-ligand constants. The newest yet unreleased version 4 should contain side chain flexibility. AutoDock has more informative web pages than its competitors and because of its free academic license, it is a good starting point when wondering into the world of molecular docking software. The AutoDock scoring function is based on the molecular mechanics force field AMBER, with two additional terms: one to model the desolvation free energy change on binding, which is based on atomic solvation parameters; and one empirical term to model the loss of conformational entropy on binding. The individual contributions to the total energy of binding, namely van der Waals, hydrogen bonding, electrostatic, desolvation, and number of rotatable bonds in the ligand, were treated as independent variables.
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