2022 DOCK tutorial 1 with PDBID 6ME2

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Introduction =


UCSF Chimera is a software which aids the interactive 3D visualization, editing, and analysis of biological macromolecules. File:Hello


(some info about DOCK)


(some info about the structure)

Required Software

(chimera, dock,...)

Seawulf: Getting Started

Basics of the Command Line/Terminal

Logging in and navigating Seawulf

File transfers to/from Seawulf

Chimera: Getting Started

Searching for/Downloading files from the PDB

The RCSB Protein Data Bank is a useful tool for searching for and downloading files containing the 3D structures of biological macromolecules. One can search for a molecule by using an exact 4 letter code (such as "6ME2") or by searching for a short description (such as "melatonin with ramelteon complex"). Note that there may be many molecules that fit a given description, so one may need to scroll through results shown after the search to find the one of interest.

(insert picture of PDB w/ search bar, results below after searching)

After finding the page for the structure of interest, one can download it in pdb or mol2 (or other) format by selecting the dark blue "Download Files" drop-down menu to the right of the page. Select the desired format, and the download will begin.

Opening and viewing PDB files

(show some screenshots and explain file types)

First-steps for visualizations in Chimera

Opening files in Chimera

Once one opens Chimera, they are met with a blue screen, and at the bottom right corner are two options called "Browse..." and "Fetch...". If the structure of interest is downloaded already to a local computer, choose "Browse..."; it is possible to download the structure from the PDB directly in Chimera using the "Fetch..." option, but note this requires knowledge of the 4-digit code for the structure listed in the PDB.

Visual configurations

Chimera can be a helpful tool for producing publication-ready visualizations of molecules. When Chimera is first opened, the structure will be drawn against a black screen; if a different appearance is desired, click the "Presets" tab at the top, where there are a number of options. A recommended preset is "Publication 1 (silhouette, rounded ribbons)".

Selecting substructures

Note that it is possible to select portions of the current structure. To do so, click the "Select" tab at the top. Options will become visible to select by chain, residue, structure, and so on. One can also hit "Control" + "Click" to interactively select a small portion of the structure. If one presses the "up" arrow on their keyboard, this will select a larger substructure containing the initial selection. Hitting "up" again will select more, until the entire structure is selected. Alternatively, hitting the "down" arrow will go backwards in selection scope, until the initial small selection is restored.

Modifying selected substructures

One of the easiest ways to make a visualization in Chimera more clear is through color editing. If one is dealing with a protein-ligand complex, for example, it may be useful to color the two structures differently to contrast the two. To do this, select one of the structures (this can be done by interactively clicking and hitting the "up" arrow, or more easily by selecting by structure), then, while the substructure is selected, click the "Actions" tab, click "Color", and make a color choice.

If one wishes to isolate specific parts of a structure from the rest, it is necessary to understand how to delete substructures. This can be done by selecting a substructure of interest, clicking "Actions", hovering over "Atoms/Bonds", then under the shown options clicking "delete" at the bottom. This will remove the selected substructure, and cannot be immediately undone, so make sure that parts of the substructure have been colored to make their separation as clear as possible to avoid deleting any parts by accident.

Saving sessions

If one wishes to save an entire session, with all configurations (such as visual orientation, focus, coloring, etc. which cannot be captures by just saving as a Mol2 or PDB file), one can go to "File" -> "Save Session As..." and this will save the current configurations.

(put in a picture?)

Organizing File Directories

It is imperative to one's ability to keep and access records, for any purpose, by having a detailed and organized directory list wherein any necessary files may be kept. While following this docking tutorial, it is recommended to have the following directories:

(insert directory list)

Dock Prep

Initial investigation/preparation

(put in here anything you notice when first opening up a sometimes messy structure--in 6ME2's case we had to remove detergents and water that were far from the of-interest binding site, handle non-standard amino acids, etc. Compare to the structure described in the literature to see if everything is accurate)

Isolating the ligand and receptor

(show how to create two separate files, one with just the ligand and one with just the receptor)

Prepping the ligand

(show how to add hydrogens/charges in the isolated ligand)

Prepping the receptor

(show how to add hydrogens/charges to the isolated receptor)

Surface Spheres

Generating DMS of receptor

(show how to get the surface/save as a DMS file)

Creating Surface Spheres

(show how to create the INSPH file in the correct directory, how to run sphgen using the INSPH file, show output).

Selecting Relevant Spheres

(show how to run sphere_selector and create necessary input file)

Generating Box/Grid

Box Generation

(show how to create showbox.in, how to run showbox)

Grid Generation

(show how to create the file grid.in, how to run grid)


Energy Minimization

Rigid Docking

Fixed Anchor Docking

Flexible Docking

Calculating Molecular Footprint

Virtual Screening

Virtual Screening Using MPI

Cartesian Minimization of Docked Molecules

Rescoring Docked Molecules