Difference between revisions of "2025 DOCK tutorial 2 with PDBID 1XMU"

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(→‎Structure Preparation)
(→‎Structure Preparation)
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'''2. Protein Receptor Preparation'''  
 
'''2. Protein Receptor Preparation'''  
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a. Generate protein structure in MOL2 format
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a. Generate protein structure in MOL2 format
  
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i. Open the downloaded pdb file (1XMU) in Chimera,  
+
i. Open the downloaded pdb file (1XMU) in Chimera,  
  
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ii. Remove ligand
+
ii. Remove ligand
  
 
  Go to Select → residue → ligand to highlight the ligand.  
 
  Go to Select → residue → ligand to highlight the ligand.  
 
Then go to Actions → Atoms/Bonds → Delete
 
Then go to Actions → Atoms/Bonds → Delete
  
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iii. Repeat the process to delete water molecules by selecting HOH instead of ligand
+
iii. Repeat the process to delete water molecules by selecting HOH instead of ligand
  
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iv. Save the protein, Go to File → Save Mol2. 1XMU_Rec_nCH.mol2 (''''n'''o' '''C'''harge and '''H'''ydrogen)
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iv. Save the protein, Go to File → Save Mol2. 1XMU_Rec_nCH.mol2 (''''n'''o' '''C'''harge and '''H'''ydrogen)
  
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b. Add Hydrogen atoms
+
b. Add Hydrogen atoms
  
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i. Go to Tools → Structure Editing → AddH. A dialogue box like this will appear, adjust as needed
+
i. Go to Tools → Structure Editing → AddH. A dialogue box like this will appear, adjust as needed
  
 
[[File:1XMU_Rec_Add H.png]]
 
[[File:1XMU_Rec_Add H.png]]
  
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ii. Select OK to proceed. If successful, You will get a confirmation message 'Hydrogens Added'
+
ii. Select OK to proceed. If successful, You will get a confirmation message 'Hydrogens Added'
  
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c. Assign appropriate charges
+
c. Assign appropriate charges
  
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i. Go to Tools → Structure Editing → Add Charge.  
+
i. Go to Tools → Structure Editing → Add Charge.  
  
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A dialogue box like this will appear, adjust as needed. For this tutorial, we will use Gasteiger charges. Leave all other settings as they are, then click OK.
+
A dialogue box like this will appear, adjust as needed. For this tutorial, we will use Gasteiger charges. Leave all other settings as they are, then click OK.
  
 
[[File:1XMU_Rec_Add Charges.png]]
 
[[File:1XMU_Rec_Add Charges.png]]
  
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ii. A new pop-up menu will appear
+
ii. A new pop-up menu will appear
  
 
[[File:1XMU_Rec_Add Charges pop-up.png]]
 
[[File:1XMU_Rec_Add Charges pop-up.png]]
  
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iii. Just as before, make sure that Gasteiger is selected. All other defaults are okay.  
+
iii. Just as before, make sure that Gasteiger is selected. All other defaults are okay.  
  
−
iv. Select OK. If successful, You will get a confirmation message 'standard charges added'
+
iv. Select OK. If successful, You will get a confirmation message 'standard charges added'
  
−
d. Go to File → Save Mol2. 1XMU_Rec_wCH.mol2 (''''w'''ith' '''C'''harge and '''H'''ydrogen)
+
d. Go to File → Save Mol2. 1XMU_Rec_wCH.mol2 (''''w'''ith' '''C'''harge and '''H'''ydrogen)
  
 
'''3. Ligand Preparation'''
 
'''3. Ligand Preparation'''

Revision as of 22:32, 5 March 2025

Introduction

Structure Preparation

The objectives of this section are:

1. Structural Evaluation 

  a. Identify any missing loops in the protein structure
  b. Assess metal coordination atoms for key interactions with the protein

2. Protein Receptor Preparation 

  a. Generate protein structure in mol2 format
  b. Add hydrogen atoms
  c. Assign appropriate charges
  d. Save the refined protein structure in mol2 format

3. Ligand Preparation 

  a. Generate ligand structure in mol2 format
  b. Add hydrogen atoms
  c. Assign appropriate charges
  d. Save the refined ligand structure in mol2 format

1. Structural Evaluation

a. Open the downloaded PDB structure in Chimera (In this tutorial, 1XMU). Check for missing loops—these appear as dashed lines in the structure.

b. There are no missing loops in the structure 1XMU, so no further action is needed.

1XMU.jpg

If you find missing loops in your structure, you will need to fix them before proceeding. Refer to (Tutorial 2025 [[1]]) for instructions on fixing missing loops.

b. In 1XMU, there is metal coordination atoms (Zinc and Magnesium) interacting with the protein. It is important to keep them intact and not delete them during protein preparation

2. Protein Receptor Preparation 

a. Generate protein structure in MOL2 format

i. Open the downloaded pdb file (1XMU) in Chimera,

ii. Remove ligand 

Go to Select → residue → ligand to highlight the ligand.

Then go to Actions → Atoms/Bonds → Delete

iii. Repeat the process to delete water molecules by selecting HOH instead of ligand

iv. Save the protein, Go to File → Save Mol2. 1XMU_Rec_nCH.mol2 ('no' Charge and Hydrogen) 

b. Add Hydrogen atoms

i. Go to Tools → Structure Editing → AddH. A dialogue box like this will appear, adjust as needed

1XMU Rec Add H.png

ii. Select OK to proceed. If successful, You will get a confirmation message 'Hydrogens Added' 

c. Assign appropriate charges

i. Go to Tools → Structure Editing → Add Charge.

A dialogue box like this will appear, adjust as needed. For this tutorial, we will use Gasteiger charges. Leave all other settings as they are, then click OK.

1XMU Rec Add Charges.png

ii. A new pop-up menu will appear

1XMU Rec Add Charges pop-up.png

iii. Just as before, make sure that Gasteiger is selected. All other defaults are okay.

iv. Select OK. If successful, You will get a confirmation message 'standard charges added' 

d. Go to File → Save Mol2. 1XMU_Rec_wCH.mol2 ('with' Charge and Hydrogen)

3. Ligand Preparation

Grid Generation

Energy Minimization

Docking

Virtual Screening

Cartesian Minimization

Rescoring and Ranking

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