2012 DOCK tutorial with Streptavidin

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For additional Rizzo Lab tutorials see DOCK Tutorials.

I. Introduction


DOCK was developed by Irwin D. "Tack" Kuntz, Jr., PhD and colleagues at UCSF. Please see the webpage at UCSF DOCK.

DOCK is a molecular docking program used in drug discovery. This program, given a protein active site and a small molecule, tries to predict the correct binding mode of the small molecule in the active site, and the associated binding energy. Small molecules with highly favorable binding energies could be new drug leads. This makes DOCK a valuable drug discovery tool. DOCK is typically used to screen massive libraries of millions of compounds against a protein to isolate potential drug leads. These leads are then further studied, and could eventually result in a new, marketable drug. DOCK is works well as a screening procedure for generating leads, but not nearly as well for optimization of those leads. Original DOCK used only rigid body docking, DOCK 4.0, however, introduced flexible ligand docking by either a)incremental construction or b)random search.

Incremental construction (aka anchor and grow) could be roughly described by a three step process: 1) rigid portion of ligand (anchor) is docked by geometrical methods 2) non-rigid segments added; energy minimized 3) the resulting configurations are 'pruned' and energy re-minimized, yielding the docked configurations

Random search method involves docking random conformations of ligand as independent rigid objects. The number of conformations allowed per rotatable bond is arbitrary and user controlled. The receptor is always held rigid in DOCK 4.0.

Streptavidin & Biotin

Streptavidin is a tetrameric prokaryoke protein that binds the co-enzyme biotin with an extremely high affinity. The streptavidin monomer is composed of eight antiparallel beta-strands which folds to give a beta barrel tertiary structure. A biotin binding-site is located at one end of each β-barrel, which has a high affinity as well as a high avidity for biotin. Four identical streptavidin monomers associate to give streptavidin’s tetrameric quaternary structure. The biotin binding-site in each barrel consists of residues from the interior of the barrel, together with a conserved Trp120 from neighbouring subunit. In this way, each subunit contributes to the binding site on the neighboring subunit, and so the tetramer can also be considered a dimer of functional dimers.

Biotin is a water soluble B-vitamin complex which is composed of an ureido (tetrahydroimidizalone) ring fused with a tetrahydrothiophene ring. It is a co-enzyme that is required in the metabolism of fatty acids and leucine. It is also involved in gluconeogenisis.

Organizing Directories

While performing docking, it is convenient to

II. Preparing the Receptor and Ligand

Downloading the PDB Structure

Preparing for DOCK with Chimera

III. Generating Receptor Surface and Spheres

Receptor Surface


IV. Generating Box and Grid



V. Docking a Single Molecule for Pose Reproduction



VI. Virtual Screening

Virtual Screening Protocol

Virtual Screening Results

VII. Running DOCK in Serial and in Parallel on Seawulf

Use PBS Queue as a reference.

Serial Calculation for Pose Reproduction

Parallel Virtual Screen

VIII. Frequently Encountered Problems