Autodock Vina Extended problem

[Sherif 0]

I have tried to redock a ligand with its receptor using Vina Extended. I set the receptor, ligand and set the grid box to the active site. But The poses i got are different from co crystallized ligand. i tried to increase the exhaustiveness but to progress.

[DmitriyMarin]

Dear @Sherif-0 ,

To explore the more possible binding modes you can increase the exhaustiveness parameter as you did and the number of modes, e.g. set exhaustiveness to 10 and the number of modes to 20 - 200.

Do you provide a ligand from a document (single ligand mode) or from a ligand file[s] (ligand library mode)?
Do your receptor and ligand have hydrogens added?

[Sherif 0]

i tried to increase exhausstivness to 50 and modes to 20 ..
i got better pose compared to original ligand but it doesnt form same interactions...
Yes i added hydrogens

[DmitriyMarin]

Ok.
If you have the ligand in the binding pocket then you can try to score the bound ligand - choose "score only" - this will compute the score of the already bound ligand. If you get this score that is quite below than the best modes that Vina produces then you will need to increase the energy range to include this scoring.
I would suggest you try the following:

• set exhaustiveness to about 10, the number of modes to about 200, increase the energy range from the default 3 kcal/mol to e.g. 6 kcal/mol (to include the score if the bound ligand), and choose to keep all the modes;
• make sure that the search box is properly positioned - whether it fully includes the binding pocket and the bound ligand;
• check if you set all the necessary rotatable bonds in the ligand;
• you might also set some side chains in the active site to be flexible but note that it might significantly increase the computational time.

The already bound state of the ligand might not be among the best modes due to multiple reasons (considering the system was well prepared for docking), among them are: 1) Vina scoring function and its weights that might be needed to be tweaked for some particular cases (e.g. increase the strength of hydrogen bonding); 2) the necessity to perform MD after docking; 3) the conformation of the crystallized ligand not corresponding to the minimum energy.

[Sherif 0]

how can I score the bound ligand?

[DmitriyMarin]

In the docking parameters of the AutoDock Vina Extended, select "Score only".

[Sherif 0]

will there be any updates for this extension ? because it is very useful but it can get better

[DmitriyMarin]

Yes, there will be updates. What would you like to be added or modified in this extension?

[Sherif 0]

well, for me, In original AD Vina, you can prepare both receptor and ligand in the software. For me now, I have to use software such as chimera to minimize the protien, add charges, hydrogens. Same for ligands. If you add this to the extension, it will be good i think.

[DmitriyMarin]

Thank you for your feedback, @Sherif-0 !

You can prepare both receptor and ligand in SAMSON as well: add hydrogens e.g. based on residue types (for neutral pH for now, but we plan on extending this functionality), minimize using the built-in Minimizer (you can minimize a ligand and a receptor in separate documents, and you can apply the option of ligand minimization before docking in AutoDock Vina Extended). As for charges, they can either be provided in the input file or set using the Edit charges editor (Edit menu > Edit charges) or directly in the Inspector for selected atoms.

What are other missing functionalities that you would like to be added? We will try to add them.

[Sherif 0]

thats great. But I can not find the minimizer

[Sherif 0]

thank you i find it...

if i think of sth,i will tell you...

May be try to add different algorithms like genetic and lamarikan

[DmitriyMarin]

Home menu > Minimize

Click on it and it will start minimization of all molecules in the document using the Universal Force Field. To stop the minimization click the second time. You can see the minimization data in the top-left corner of the Viewport.

[DmitriyMarin]

Please note that the minimization of a big protein might take some time. You can also use the Gromacs Wizard for protein minimization.

[Sherif 0]

thanks so much.. i am enjoyng this software

[DmitriyMarin]

Thank you, @Sherif-0 , for your feedback!

[Sherif 0]

Hi

i think you can add the parameters same as present in AD Vina.. like number of seed generations, the algorithm used , etc...

[DmitriyMarin]

@Sherif-0 ,

We will add the seed number in the next version. What do you mean by specifying the used algorithm?

[Sherif 0]

well i was mistaken i am sorry

[DmitriyMarin]

Thanks for the reply. No problem!