Note: Seeking complete tutorials and/or guidance on performing Molecular Docking and Molecular Dynamics (MD) simulation using the following software.
Softwares: PyRx, Pymol, Molecular Operating Environment (MOE), Schrodinger Suites, server-based softwares, etc.
Introduction: In the field of molecular modeling, docking is a method that predicts the preferred orientation of one molecule to a second when bound to each other to form a stable complex. Knowledge of the preferred orientation, in turn, may be used to predict the strength of association or binding affinity between two molecules using, for example, scoring functions. The associations between biologically relevant molecules such as proteins, peptides, nucleic acids, carbohydrates, and lipids play a central role in signal transduction. Furthermore, the relative orientation of the two interacting partners may affect the type of signal produced (e.g., agonism vs. antagonism). Therefore, docking is useful for predicting both the strength and type of signal produced. Molecular docking is one of the most frequently used methods in structure-based drug design due to its ability to predict the binding conformation of small-molecule ligands to the appropriate target binding site. Characterization of the binding behavior plays an important role in the rational design of drugs and elucidating fundamental biochemical processes.
Molecular dynamics (MD) is a computer simulation method for analyzing the physical movements of atoms and molecules. The atoms and molecules are allowed to interact for a fixed period, giving a view of the dynamic "evolution" of the system. In the most common version, the trajectories of atoms and molecules are determined by numerically solving Newton's equations of motion for a system of interacting particles, where forces between the particles and their potential energies are often calculated using interatomic potentials or molecular mechanics force fields.
Therefore, it would be great to have guidance from the experts in these areas on how to perform Molecular Docking and Molecular Dynamics simulation.
Thank you very much for your consideration.
Dear Saikat,
For drug designing/protein studies, these platforms/techniques you mentioned are being used.
I will suggest you read research papers and books to have the proper knowledge.
Anyhow, the PyMol is a product of Schrodinger under an open-source licence and being used for visualisation and some structural analysis to editing the proteins. Schrodinger suite is being used for multiple purposes. Still, the Maestro is a suite itself having packages for protein preparation, ligand preparation, docking (glide), Admet (quikprop), to MD simulation using DE show's Desmond that also provides visualisation of trajectories and RMSD, RMSF and other results and the MOE does the same.
Pyrx also software for Molecular docking.
Shaban Ahmad
Thank you very much for your insightful comment.
It would be great if you mention/provide information on - protein preparation, ligand preparation, docking (glide) as mentioned below:
- The parameters one should follow during protein (macromolecule) preparation and ligand preparation (using Maestro, or MOE, or PyRx, or DS Visualizer)
- Performing Molecular Docking and setting up the Grid-Box
- Analyzing Molecular Docking results and visualization (using like LigPlot plus etc.)
- Parameters must be followed during Molecular Dynamics simulation and analyzing the RMSD, RMSF values
On the other hand, I get stuck while setting up the Grid Box using PyRx (AutoDock Vina wizard). What should I need to follow performing the docking using PyRx though setting up the Grid Box properly.
Thank you very much.
"Therefore, it would be great to have guidance from the experts in these areas on how to perform Molecular Docking and Molecular Dynamics simulation"
Every Docking software work on a different algorithm. Partially same goes for simulation software. Each workflow needs to be tuned according to your need, and therefore there is no single workflow that will work for all of them.
For most of the software, tutorials are already available on the internet.
And, as Shaban Ahmad mentioned, you need to go through research papers that match your requirement. The parameters, grid box e.t.c are mentioned in most of the papers.
If you are getting stuck in some particular software/step, mention that step and also mention the error you are getting.
Rajesh Pal
Thank you very much for your kind time and consideration.
I would like to have guidance/tutorial on MOE (v. 2015.10), or Schrödinger (v. 2017.2) for M. Docking and Dynamics.
Thank you very much.
For Schrodinger:
Did you try their Youtube channel?
https://www.youtube.com/user/SchrodingerLLC
They cover almost all the topic
Dear Abu Saim Mohammad Saikat
If you have access to Schrodinger, you will get proper protein and ligand preparation guidance on Schrodinger TV on youtube.
For Gridbox, you first need to have a binding pocket. You can get it using sitemap in maestro itself and then generate a bigger grid to the sitemap result or click on sitemap it will take automatically.
To analyse the results, you can use any software, including the famous one name PyMol or even use a ligand interaction diagram to visualise the 2D graphics.
For dynamics, you need to have proper knowledge of all the things and your complex too.
I hope you must have got a fundamental that might help you.
Rajesh Pal
Thank you very much for providing the YouTube channel.
I have tried to go forward following the guidance from the youtube channel videos but the situation appeared difficult compared to my version of Schrödinger (v. 2017.2).
Shaban Ahmad
Thank you very much for your useful information.
I followed the youtube channel. But it seems a bit challenging while performing my version of Schrödinger (v. 2017.2); Maestro (v.11.2).
Protein preparation (wizard):
- After removing water molecules and all the heteroatoms, I tried to perform the Optimization and Minimization (force field - CPLS3e), but resulted error. Do you know any possible reasons?
Thank you!
Rajesh Pal
I performed preprocess first, then removed the unnecessary Chain, Water atoms, and Hetero molecules. After that, the Optimization and Minimization were performed.
Is that OK? Or I need to do it another way?
Thank you!
During protein pre-process optimisation, have you added charges?
While working with MOE or Autodock, we add Partial or Kollman charges...
If undertaken, then it's fine. If not kindly check this step.
Arundhati Mehta
Thank you very much. I will recheck and inform you.
That generally does not happen. Because the workflow is pretty much straightforward. Do you have the trial version or full version of the software?
If you have the full version, contact customer care, they will help you out using a remote connection.
Rajesh Pal Shaban Ahmad Arundhati Mehta
Thank you very much for your useful information.
How can I save the output file after docking (protein-ligand complex) in the .pdb file? (Please find the attached photo as a reference). It's showing an error when I am trying to save it.
Thank you very much.
Select the docked protein and ligand in the workspace and merge them. You will get a single merged file which you can name and save by PDB extension by selecting the "Files of type: By Extension".
Dear Saikat,
First, select both protein and ligand, right-click on the mouse, then select merge; this will generate a single protein-ligand complex.
Now select the new complex which you've obtained after merging. Now go to file and export structures and save it to PDB.
Shaban Ahmad Rajesh Pal
It would be great if you kindly address the following issues:
How can I fix the problem performing the MD Simulation by using the Desmond? It is showing the only option "Localhost4" rather than any Linux Host. How can I fix this? (please find the attached photos for references).
Thank you very much.
Dear Saikat,
The Desmond can only run on Linux operating system, and it only supports on Tesla GPU (please check the version/model from Schrodinger/desmond website) also you can have one option to submit the job on server using its own remote.
Shaban Ahmad
Thank you very much for your reply.
Is there any possible way to run Desmond (Schrodinger Suites) from Windows PC?
Thank you!
That's not true at all Shaban Ahmad . You can also run Desmond on a low-end GPU. Of course, there will be a performance issue but it can get your job done.
I have personally used GeForce GT 730.
Dear Rajesh Pal,
Is it true that one can run Desmond only with Tesla GPU? I do have a Ti2080 GPU, can I use Desmond?
Thanks in advance
Rajesh Pal, The protein structure was prepared by removing water atoms, hetero atoms and adding polar hydrogen atom and kollman charges on it.
Mahbubul Himel As I mentioned, that's not true at all. One can run Desmond in low end GPU as well
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