Difference between revisions of "2024 DOCK tutorial 3 with PDBID 1Y0X"

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(Created page with "= Introduction = == Learning Objectives == == Setting Up Your Environment == == Downloading a protein from the PDB database == = Preparation of the ligand and protein =...")
 
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= Introduction =
 
= Introduction =
 +
 +
#Setting up your environment
 +
#Downloading a protein from the PDB database
 +
#Determining if there are any missing loops in the structure and if they need to be modeled
 +
#Preparing the ligand
 +
#Preparing the protein
 +
#Finding the binding site of the protein
  
  
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== Downloading a protein from the PDB database ==
 
== Downloading a protein from the PDB database ==
 +
 +
 +
  
 
= Preparation of the ligand and protein =
 
= Preparation of the ligand and protein =
 +
#Evaluate the structure to determine if there are any missing loops
 +
#Prepare the protein structure
 +
#Prepare the ligand structure
  
 
=== Evaluating the Structure===
 
=== Evaluating the Structure===
 +
 +
#Select an atom at near the start of the missing section (hold the ctrl button while clicking it)
 +
#Select another atom near the binding site (hold ctrl + shift while clicking the second atom)
 +
#Go to Tools → Structure Analysis → Distances
 +
 +
 +
===Preparing the Protein file===
 +
#Select an atom on the protein
 +
#Press the up arrow until the entire protein is selected
 +
#Go to Select → Invert (all models).  This will change the selection from the protein to everything else in the structure
 +
#Go to Actions → Atoms/Bonds → Delete
 +
#Save the structure with a new file name (i.e. 4s0v_protein_only.pdb).  Your pdb file will now look similar to this:
 +
#Adding hydrogens
 +
#Adding charge
 +
#Click on one atom anywhere on the protein
 +
#Click on Select → Zone.  This will cause the following dialogue box to appear:
 +
===Preparing the Ligand File===
 +
#Select an atom on the ligand
 +
#Press the up arrow until the entire ligand is selected (you may have to press the up arrow many times)
 +
#Go to Select → Invert (all models).  This will change the selection from the ligand to everything else in the structure
 +
#Go to Actions → Atom/Bonds → Delete
 +
#Save the structure with a new file name (i.e. 4s0v_ligand_only.pdb).  The image will look similar to this:
 +
 +
#Add hydrogens
 +
#Add charges
 +
 +
 +
===Final Steps===
 +
 +
=Creating the Protein Binding Site Surface=
 +
 +
===Creating the Required Surface (DMS) File===
 +
 +
 +
===Generating Spheres for the Binding Site===
 +
 +
===Binding Site Spheres===
 +
 +
#scp selected_spheres.sph to your local computer
 +
#Close any open sessions you have in Chimera
 +
#In Chimera open selected_spheres.sph
 +
#In the current session, open the original protein/ligand complex (4s0v.pdb)
 +
#You should see the spheres located within the binding site of the protein, similar to:
 +
 +
#Hold down ctrl and click on a sphere
 +
#Press the up arrow until all spheres are selected
 +
#Actions → Atoms/Bonds → hide
 +
#Verify the ligand is where the spheres were
 +
 +
 +
=Box and Grid Generation=
 +
===Generating the Box===
 +
===Generating the Grid===
 +
 +
=Energy Minimization=
 +
 +
===Ligand Minimization===
 +
=== Footprint Analysis===
 +
=DOCK=
 +
===Rigid Docking===
 +
===Flexible Docking===
 +
= Virtual Screening of a Ligand Library =
 +
=Cartesian Minimization of Virtually Screened Small Molecules=
 +
=Rescoring and Ranking Virtually Screened Molecules=

Revision as of 22:11, 17 March 2024

Introduction

  1. Setting up your environment
  2. Downloading a protein from the PDB database
  3. Determining if there are any missing loops in the structure and if they need to be modeled
  4. Preparing the ligand
  5. Preparing the protein
  6. Finding the binding site of the protein


Learning Objectives

Setting Up Your Environment

Downloading a protein from the PDB database

Preparation of the ligand and protein

  1. Evaluate the structure to determine if there are any missing loops
  2. Prepare the protein structure
  3. Prepare the ligand structure

Evaluating the Structure

  1. Select an atom at near the start of the missing section (hold the ctrl button while clicking it)
  2. Select another atom near the binding site (hold ctrl + shift while clicking the second atom)
  3. Go to Tools → Structure Analysis → Distances


Preparing the Protein file

  1. Select an atom on the protein
  2. Press the up arrow until the entire protein is selected
  3. Go to Select → Invert (all models). This will change the selection from the protein to everything else in the structure
  4. Go to Actions → Atoms/Bonds → Delete
  5. Save the structure with a new file name (i.e. 4s0v_protein_only.pdb). Your pdb file will now look similar to this:
  6. Adding hydrogens
  7. Adding charge
  8. Click on one atom anywhere on the protein
  9. Click on Select → Zone. This will cause the following dialogue box to appear:

Preparing the Ligand File

  1. Select an atom on the ligand
  2. Press the up arrow until the entire ligand is selected (you may have to press the up arrow many times)
  3. Go to Select → Invert (all models). This will change the selection from the ligand to everything else in the structure
  4. Go to Actions → Atom/Bonds → Delete
  5. Save the structure with a new file name (i.e. 4s0v_ligand_only.pdb). The image will look similar to this:
  1. Add hydrogens
  2. Add charges


Final Steps

Creating the Protein Binding Site Surface

Creating the Required Surface (DMS) File

Generating Spheres for the Binding Site

Binding Site Spheres

  1. scp selected_spheres.sph to your local computer
  2. Close any open sessions you have in Chimera
  3. In Chimera open selected_spheres.sph
  4. In the current session, open the original protein/ligand complex (4s0v.pdb)
  5. You should see the spheres located within the binding site of the protein, similar to:
  1. Hold down ctrl and click on a sphere
  2. Press the up arrow until all spheres are selected
  3. Actions → Atoms/Bonds → hide
  4. Verify the ligand is where the spheres were


Box and Grid Generation

Generating the Box

Generating the Grid

Energy Minimization

Ligand Minimization

Footprint Analysis

DOCK

Rigid Docking

Flexible Docking

Virtual Screening of a Ligand Library

Cartesian Minimization of Virtually Screened Small Molecules

Rescoring and Ranking Virtually Screened Molecules

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