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MobleyLab / benchmarksets

Benchmark sets for binding free energy calculations: Perpetual review paper, discussion, datasets, and standards
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Add info on bromodomain benchmark #36

Closed GHeinzelmann closed 7 years ago

GHeinzelmann commented 7 years ago

Hi. I have finished writing the inroduction and the free energy calculations on BRD4(1), the only thing left now is choosing the benchmark ligands and creating the Table. I thought it would be good to have a checkpoint now, to see if everything is going in the right direction. Best,

Germano

davidlmobley commented 7 years ago

Thanks! I'm dealing with a grant proposal right now but will try to have a look as soon as I can. Or @mkgilson can look too...

GHeinzelmann commented 7 years ago

No worries! I'll start looking into the ligands to include in the mean time! Best,

Germano

mkgilson commented 7 years ago

Thanks Germano! I will try to look this weekend. I am straining to finish editing the D3R GC2 overview paper, which is already late!

Best, Mike

On 6/29/2017 11:25 AM, GHeinzelmann wrote:

Hi. I have finished writing the inroduction and the free energy calculations on BRD4(1), the only thing left now is choosing the benchmark ligands and creating the Table. I thought it would be good to have a checkpoint now, to see if everything is going in the right direction. Best,

Germano

    You can view, comment on, or merge this pull request online at:

https://github.com/MobleyLab/benchmarksets/pull/36

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GHeinzelmann commented 7 years ago

OK, just a small correction, sorry about that. It turns out some of the ligands of BRD4(1) are not neutral, so in the part that says that "all of the ligands are neutral" can be changed to "most ligands are neutral", or maybe something similar. Best,

Germano

davidlmobley commented 7 years ago

@GHeinzelmann - I am starting to look at this. I took the liberty of: a) Changing the title of the PR to reflect what this is doing b) moving your "benchmarksets[WIP].pdf" and ".tex" to "benchmarksets.pdf" and "benchmarksets.tex"; be sure to "git pull origin GHeinzelmann" to pull down these changes

The reason (b) is appropriate is that you aren't actually changing these files until I agree to it, you're just PROPOSING changing them. So it's totally fine to make that proposal. AND, changing the ACTUAL FILES will make it so GitHub will show me what you're changing in the files (see "files changed" tab above!) in a useful way, rather than showing me that you've introduced two new files which consist of entirely new content.

davidlmobley commented 7 years ago

@GHeinzelmann - it looks like things are headed in the right direction, though I still need to have a look at whether organization of this is consistent with the other benchmarks. But on the whole the content seems solid and worthwhile, which I very much appreciate!!

I left some comments for you to look at when you have time, and potentially incorporate in an update to this PR.

I will probably also go through the parts you have written and make some edits to grammar/style and submit a PR to from my branch to your branch (so that you can review/merge it and then it will update this PR). But that probably won't be for a day or two, so in the meantime, please proceed!

One other thought -- if you're up for it, once you have this written up, it would probably be good to ask Matteo Aldeghi or Phil Biggin to have a look over it as sort of an informal peer review.

Oh, finally -- your PR should also add yourself as an author!

Thanks again for your contribution.

davidlmobley commented 7 years ago

@GHeinzelmann - how does this stand? Do you think it's ready to merge? I'll have some time in transit this week (part of it is today) and hope to review your changes to finalize, if you think it's done.

GHeinzelmann commented 7 years ago

Hi. I think pending a final review it is ready, After I got the openeye license I have redone the ligand table figures and also got the smiles for each molecule. I just could not find the PubChem ID for two of them, but the rest is all there. I was waiting for some feedback on the ligands before I uploaded the structures, but since we are merging soon I'll do that part now so everything is ready.

GHeinzelmann commented 7 years ago

BTW the last version is on the GHeinzelmann branch.

davidlmobley commented 7 years ago

I was happy with the ligand choices.

davidlmobley commented 7 years ago

@GHeinzelmann - I spotted one more issue. I can't parse the SMILES string for Cc1c(sc-2c1C(=N[C@H(c3c2c(no3)C)CC(=O)N)c4ccc(cc4)Cl)C , "Compound 3". Can you re-check please? It doesn't parse with my tools.

I did find a PubChem compound ID for RVX-OH, the other one where you were missing an ID, so this is the last one remaining.

GHeinzelmann commented 7 years ago

OK, thanks for finding the PubChem ID for that compound, sorry I could not find it myself but I did try :). About the smiles for compound 3, I just rechecked and it it renders the 2D structure correctly, so not sure what could be the problem. I am pasting it again directly from the input file of the openeye 2D rendering:

Cc1c(sc-2c1C(=N[C@H](c3c2c(no3)C)CC(=O)N)c4ccc(cc4)Cl)C

It looks the same as the one you wrote, except for the [C@H part, which seems to be missing a closure bracket in yours. I just checked the paper table and it is written the same way as above, so that might fix it.

GHeinzelmann commented 7 years ago

Aside from that, I am creating all the ligand and solvated structures to include in the input_files and that part will be finished today.

davidlmobley commented 7 years ago

Ah, you seem to have nailed it, @GHeinzelmann . The string I'm seeing in the LaTeX file AND on GitHub is Cc1c(sc-2c1C(=N[C@H(c3c2c(no3)C)CC(=O)N)c4ccc(cc4)Cl)C which is missing the close square bracket after the C@H, but the string you just pasted, Cc1c(sc-2c1C(=N[C@H](c3c2c(no3)C)CC(=O)N)c4ccc(cc4)Cl)C, as that and parses properly. Can you fix?

And, yeah, for some reason I can't find this one in PubChem, which is odd... So, we have to leave N/A for that one for now.

GHeinzelmann commented 7 years ago

Yes I'll fix that no problem. The .tex version I have here has the bracket, so it is possible that I accidentally erased it when I had the GitHub window open. Sorry about that.

GHeinzelmann commented 7 years ago

I think we are all set and ready to merge. I figured I would add myself as a second author, not sure if that is the idea but it can be easily changed if needed. The input files and the README.md file are in the input_files/BRD4 folder, following Niel's organization in his branch. I have also addressed the review comments in the new .tex and .pdf versions of the main paper. I think I have covered everything that was missing, but let me know if there is anything else to be done. I think it all looks good, thanks for inviting me to contribute to the paper!

davidlmobley commented 7 years ago

@GHeinzelmann - great, thanks! I'll take a final look. I just need to hear back from Mike...

GHeinzelmann commented 7 years ago

Hi. I have updated the paper in my branch with the latest comments from @mkgilson, also changing a little the bit the information on Compound 4 and Compound 8a in Table 7 and in the section where we discuss this Table (last paragraph of subsection 1). For now I have kept these two ligands in the benchmarks, discussing the docking of Compound 8a (and the similarity to the pose of Compound 4) in the README from the input_files/BRD4 folder.

davidlmobley commented 7 years ago

I'm running behind on the e-mail thread/updates here but hope to review this and get everything merged by the end of the week. Thanks for all your work on this!

davidlmobley commented 7 years ago

@GHeinzelmann - congratulations, it is merged! You're now an author. :) Thanks for all your work on this.

GHeinzelmann commented 7 years ago

That's great! Thanks for the reviews and the opportunity!

mkgilson commented 7 years ago

:-)

On 8/4/2017 1:12 PM, David L. Mobley wrote:

@GHeinzelmann https://github.com/gheinzelmann - congratulations, it is merged! You're now an author. :) Thanks for all your work on this.

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