Revision as of 16:37, 10 February 2020

This tutorial teaches you how to dock a drug molecule to a receptor.

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I. Introduction

4F4P

4F4P is the crystal structure of Tyrosine Kinase SYK in complex with ligand LASW836. You can get the pdb file from here [1]. The resolution is 2.37 Å. Click Download Files -> PDB Format to download PDB file. File:Example.jpg

Checking the structure

Read the article related to the PDB file [2] to understand protonation states, charges and other important information regarding the receptor and the ligand.

Open the pdb file through chimera and look at the structure.

Identify the main components of the model (receptor, ligand, solvent, cofactors). In our case, the protein contain one chain, ligand cofactor sulfate(SO_4) and water HOH.

Prepare the Receptor file

In this part we are going to generate the receptor file and the ligand file.

With the pdb file loaded by chimera, do Select -> Residue -> SO4 to select the sulfate. Use Actions -> Atoms/Bonds -> Delete to delete it. Then do Select -> Residue -> HOH to select the water molecules. Use the same method to delete it. Then do Select -> Structure -> ligand to select ligand molecule. Use the same method to delete it. Save the receptor as 4f4p_rec_noh.mol2.

[[File:]]

Prepare the Ligand File

Open the pdf file again. Do Select -> Structure -> ligand to select the ligand. Do Select -> Invert (all models), then delete the selected atoms. This will left the ligand molecule only. Save it as 4f4p_lig_noh.mol2.

[[File:]]

Adding hydrogen and charge

Now we are going to add hydrogen atoms and charges to our receptor and ligand. Open 4f4p_rec_noh.mol2 file using Chimera and use the following instructions to prepare the receptor file to be used in DOCK. Tools -> Structure editing -> AddH. This command will add hydrogen to the receptor. Tools -> Structure editing -> Add Charge. This command will add charge to atoms to make the receptor neutral. Save the file as 4f4p_rec_h.mol2

Open 4f4p_lig_noh.mol2, follow the same steps for ligand file, add hydrogen. The Chimera added 2 hydrogens to the nitrogen where it is supposed to be only one, as referred in the pdb report. So remove one hydrogen . (Hold Cntr and select extra H, then Actions -> Atoms/Bonds -> delete.) After removing hydrogen add charges to the ligand Tools -> Structure editing -> Add Charge. After this save the file as 4f4p_lig_h.mol2.