[Chimera-users] Doubts about DOCK6.9 and ZINC20

[Elaine Meng]

Hi Francesca,
Most of these are DOCK and ZINC questions.  We are not experts in DOCK or ZINC so I can only try to answer a few things related to Chimera specifically, and some of my answers are only guesses.  You should look at the DOCK and ZINC websites, and if you can't find the answer there, ask these questions using their help addresses or mailing lists, if any.

<http://dock.compbio.ucsf.edu/>
<http://dock.compbio.ucsf.edu/Contact_Info/index.htm>

<http://zinc20.docking.org/>

How to save the receptor depends on what you are using it for.  If you are saving the receptor from dock prep before doing the docking or calculating scoring grids with DOCK, then 
(a) transformed or not doesn't matter unless  you have a bunch of different receptors that you matched to each other and you want them all to stay matched up to each other for easy comparison of their docking results
(b) whether you need mol2 or pdb, I don't know: read the instructions for DOCK, whichever parts of the program where you are going to use that receptor file as input.  If the tutorial does it one way and you are doing steps similar to the tutorial, might as well do it the same way as the tutorial says.  It might be OK either way.
(c) if DOCK is using the charges from Chimera, then yes it is a mistake to remove the hydrogens because they have charges on them just like all the other atoms.  If you remove them then the protein will have super-negative net charge because you removed hundreds of positively charged atoms.

How to save the ligands before docking depends on the docking options and program.
(a) whether you need SETS or not in the mol2 file, see the DOCK manual.  My guess is that you don't need it for rigid docking, and that it is only used with certain DOCK flexible docking options.
(b) I don't know whether DOCK uses the sybyl-style hydrogen names or not, or if it even matters. We added this option a long, long time ago for people who were actually using the program SYBYL.

How to view so many docking results: Normally people just save the "top N" results (say 1000 best-scoring molecules) and only look at those, and they may also have to split it up into smaller sections (say 5 files of 200 molecules each) depending on how many their computer can handle at once.

I hope this helps,
Elaine
-----
Elaine C. Meng, Ph.D.                       
UCSF Chimera(X) team
Department of Pharmaceutical Chemistry
University of California, San Francisco

> On Jul 20, 2021, at 12:14 AM, Francesca Magarotto - francesca.magarotto2--- via Chimera-users <chimera-users at cgl.ucsf.edu> wrote:
> 
> Hi,
> I’m a student and I’m currently doing a thesis. 
> I’ve never used Dock or Chimera before, so I followed some tutorials but now I’m a bit confused. 
> 1. For five months I’ve saved the prepared receptors and the ligands as mol2, but I didn’t choose “write current selection to @SETS section of file”.
> I’ve just read on Chimera that it “makes the currently selected atoms as a SET (as used to specify the rigid portion of a ligand in DOCK)”. The docking I’ve performed seemed to go, but is actually everything wrong because I didn't select the option? 
> 2. I’ve generated the receptor without hydrogens after dockprep (so after assigning charges and hydrogens). I’ve deleted only hydrogens but maybe the charges are still there, is that an error?
> 3. I’ve always saved the receptor without hydrogens in mol2 instead of pdb, because I’ve seen this in some tutorials, but now I’ve read tutorials that save it in pdb. 
> Is this another error? 
> I was able to generate the surface even with mol2 no hydrogens receptor and I’ve always toggle on “use untrasformed coordinates”, but obviously the options to save the file change for mol2 and pdb.
> 4. I follow a tutorial online to download 3D molecules from ZINC20. Anodyne means there are no PAINS and no reactive groups? Is the most “clean” reactivity pattern?
> 5. I don’t know how to organize all the directories and subdirectories downloaded with ZINC. I downloaded them in format mol2 and method curl, is that correct or shoul I use fot the virtual screening another format and method?
> To perform a virtual screening, I need to save them in a single mol2 file? How can I do that without errors? I've seen the option "flat" in downloading method in ZINC, is this a way to download the molecules correctly for virtual screening?
> 6. I need to use Chimera, but even with ViewDock I’m not able to open so many molecules (190 822), how can I look at the results in the end? 
> 7. I’ve saved the ligands’ mol2 files using sybyl-style hydrogen naming. Is that an error?
> 8. To perform the virtual screening using 3D molecules from the tranche browser of ZINC20, can I use them as they are or I need to edit them in some way (for example after downloading them, open them in Chimera and using add H and/or add charge)? 
> I need very specific indications about all these questions, because I’ve never done something similar, it’s the very first time with all and I’m afraid of making mistakes.
> I apologize for the many questions, but I hope that someone can answer all my doubts. 
> Thank you, 
> Francesca. 
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