2021 DOCK tutorial 2 with PDBID 2ZD1

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This tutorial will allow the student to perform a virtual screen of a large number of ligands to a target through the use of molecular docking. The student will also learn how to visualize the starting ligand and receptor along with the resulting docked ligand poses.


Virtual Screening

Molecular Docking


The DOCKING program specifically computes the interaction energy between the receptor and candidate ligand at different orientations. The ligand with the highest activity (usually the ideal candidate for a synthetic ligand or drug) would have the lowest computed energy.

Docking algorithms can be broadly classified as flexible (anchor and grow) or rigid. A rigid docking algorithm begins with a fully-formed ligand (whose structure is obtained from experiment) and allows for sampling of the rigid placement of the given experimental pose in the binding site of the receptor while varying the translational and rotational degrees of freedom of the whole ligand within the three spatial dimensions. Internal angle rotational degrees of freedom are not explicitly sampled with basic rigid docking.

Traditional flexible docking starts with a ligand scaffold, which is usually the largest substructure in a ligand, identified as such after the molecule is divided into substructures at its rotatable bonds. By a chosen method, such as Monte Carlo sampling or simulated annealing, multiple poses of this “anchor” substructure are then generated within the receptor binding pocket and scored. The next substructure’s layers of atoms are then added to the most favorable subset of initial anchor poses, and the process repeats until all the molecule is fully rebuilt within the receptor. This on-the-fly flexible conformer growth and minimization process is known as “anchor and grow.”

'Conformal space search' A sequence of complexes of receptors and ligands in specific poses are constructed for subsequent evaluation by a set of scoring functions.


Docking Assessment

Tools and Platforms

Protein DataBank https://www.rcsb.org/structure/2zd1

Chimera https://www.cgl.ucsf.edu/chimera/



DOCK 6.9 is one of the many tools available to computational biologists that predicts ligand binding geometries and interactions. The functions of DOCK 6.9 are diverse and have several general applications. A primary use of the program involves a virtual screening of thousands of molecules for an intended purpose. These purposes can include database screenings for molecules that inhibit enzyme activity, bind a particular protein, or even bind to larger complexes. As more versions of the program are released, new features are added such as the inclusion of solvation and receptor flexibility considerations in its calculations.


2ZD1 is the PDB code for the catalytic complex between human HMG-CoA reductase (HMGR) and Simvastatin. HMGR is considered a rate-controlling enzyme in the metabolic pathway responsible for the biosynthesis of cholesterol. Inhibitors of HMGR, known as statins, are often prescribed as treatment therapies for high cholesterol patients. While statins inhibit the catalytic effect of HMGR, they also provide other positive biochemical effects such as the stimulation of bone growth and anti-inflammatory responses. Studying statin binding using this complex can potentially aid in the discovery of drugs capable of producing these off-target effects.

File and Directory Preparation

Before beginning the actual docking procedure, we will create a set of directories to store the various files we will be generating in an organized manner. We will also download the initial PDB file for our protein from the RCSB.

  1. Navigate to the personal student directory for AMS 536: /gpfs/projects/AMS536/year/students/name