Tutorial
This is the tutorial page for the MORLD web service.
Follow the tutorial step by step.
This is the tutorial page for the MORLD web service.
Follow the tutorial step by step.
In this tutorial, we will optimize the compound, ponatinib, to generate novel inhibitors against the target protein, DD1 kinase. You can download the prepared pdb file of DDR1 kinase here.
According to Autodock Vina, Ponatinib shows the binding energy around -13.1 kcal/mol against DDR1. Using MORLD, We will decrease the binding energy of the initial molecule, ponatinib, against DDR1.
If you want to check the result of demo quickly, please refer to the JobID #1 at Queue page.
Insert the canonical SMILES string of ponatinib at the text field of "Initial molecule".
CC1=C(C=C(C=C1)C(=O)NC2=CC(=C(C=C2)CN3CCN(CC3)C)C(F)(F)F)C#CC4=CN=C5N4N=CC=C5
Insert the binding site information. The given values are derived from PDB ID:3ZOS and ADT (AutoDockTools).
Center x: -7.5
Center y: 2.5
Center z: -40
Size x: 24
Size y: 20
Size z: 20
Click the "Submit" button and check the job has been submitted at "Queue" page.
With the default setting, it will takes about two days. If you want to run a test trial, reduce the parameter "Max num. of modification" or "Num. of training episode".
Check the submitted job at "Queue" page.
waiting: The job has been successfully submitted and is waiting in the queue to be prepared for execution.
prepared: The system has created a directory for the job and moved the necessary files. The job is now fully prepared and will start as soon as computing resources become available.
running: The job is successfully running on the server.
finished: The job is finished and you can download the result file.
failed: The job is stopped by error. Please check the input information whether it is entered correctly.
If the job has finished successfully, then the Download link of the result will appear.
Inside the download file, you will find below files and folder.
This files contains all the optimized molecules. The number of optimized molecules are the same as the number of training episode. If you set the number of training episode as 5000, then there are 5000 optimized molecules in "optimized_total.txt" file.
Each column represents the generated number, SMILES code of the generated molecule, binding energy (Qvina score), SA score, and QED score respectively. With this data, you can sort by the binding energy to find the highest binding affinity molecule. Or set the minimum SA score to filter the irrational structure of the optimized molecules.
This file is a log of the MORLD model. It shows in what order the molecules are modified at each Episode.
This folder contains the files of binding pose of the optimized molecule. Each file is named as "pose_##.pdbqt" where ## is the generated number. You can see the binding pose of the highest docking score molecule in "optimized_total.txt" file by checking the generated number.
You can open .pdbqt file and see the binding pose with the target protein with visulization tool such as Pymol.
This file is contains the input paremeters of the job.
This is a guide on troubleshooting steps for when a job fails
[Possible Error Messages]
"The SMILES string of your input molecule, your_input_SMILES, is invalid. Please check and enter a valid SMILES format file."
"The SMILES string of your input molecule, your_input_SMILES, cannot be converted to a PDBQT file format with openbabel. Please check your input molecule."
[Solutions]
Please check if the format of the SMILES you entered is correct, and verify whether it can be converted to a PDBQT file using OpenBabel.
[Possible Error Messages]
"Obabel timeout error: Stereochemistry is wrong, using the distance geometry method instead.
[Solutions]
This error occurs because OpenBabel encountered an error while generating a 3D structure from the SMILES. Please check the stereochemistry information in your input SMILES. If the stereochemistry information is not important, please try converting it to canonical SMILES format and input again.
[Possible Error Messages]
"The pdb file you uploaded cannot be converted into pdbqt file. Please check your pdb file."
[Solutions]
This error means that the input PDB file cannot be converted to a PDBQT file. Please verify that your PDB file is correct.
[Possible Error Messages]
"Cannot calculate docking scores. Please check your docking configurations; binding pocket size or location."
[Solutions]
This error occurs when QuickVina does not execute properly. While there are various causes for this error, you can check the followings:
1. Verify that the location of binding box is correctly set. Check if the coordinate values you entered match the pocket location in the receptor protein's PDB file.
2. Confirm that the binding box size is appropriate. Errors may occur if the binding box size is too large or too small. The search space volume should not exceed 27000 Angstrom^3.
In addition to the errors mentioned above, we are taking measures to address other errors that may occur. If you experience difficulties in resolving an issue, please contact the server manager, and we will provide assistance.