ADL: autodock Digest, Vol 139, Issue 4

Michel Sanner sanner at scripps.edu
Sun Mar 6 16:13:28 PST 2016


Dr. Steinberg,

Looking back through your history on the mailing, to my mind, the most 
salient point about your emails
is precisely their lack of  nuance and tact as many on the mailing list 
probably knew. So, why are we to read them ?.
I decided I don't.


On 3/6/16 12:00 PM, autodock-request at scripps.edu wrote:
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> Today's Topics:
>
>     1. Re:  Question about AutoDock tools! (sandra)
>     2.  Could n't open "ligand_out.pdbqt" for writing (soumi )
>     3. Re:  Question about AutoDock tools! (Richard  Wood)
>     4.  ADFR (Dr. Yaron Steinberg)
>
>
> ----------------------------------------------------------------------
>
> Message: 1
> Date: Sat, 5 Mar 2016 21:22:57 +0200
> From: sandra <sandra at theindoleshop.com>
> Subject: Re: ADL: Question about AutoDock tools!
> To: autodock at scripps.edu
> Message-ID: <56DB3211.5070906 at theindoleshop.com>
> Content-Type: text/plain; charset=windows-1252
>
> Thank you, I was able to create a .pdb file for the ligand d-ETH-LAD.
> However I did not do any conformational distribution, all I did was draw
> out the D-siomer in a 2D sketch, and converted it into a 3D .pdb file.
> When I uploaded the .pdb file into AutoDock Tools, it worked--to the
> extent that it loaded the proper 3D orientation, and it was the right
> isomerization.
>
> However, in AutoDock Tools, when i selected grid>set map ypes>choose
> ligand, and selected the ETHLAD, it says it didnt work because it only
> reads pdbqt files!
>
> MarvinSketch seems to not have any option to save in .pdbqt format. So I
> tried converting the pdb file into pdbqt using OpenBabel, a conversion
> software. However, when I tried uploading the converted pdbqt ligand
> file into AutoDock Tools (by selecting ligand>input>open), it says it
> cant read it!
>
> It seems there was a problem when converting the .pdb file to .pdbqt. Is
> there an extra step i need to do in either OpenBabel or MarvinSketch? I
> will read over the link you just sent me. Thank you so much~
>
> Best regards! :)
>
> On 3/5/2016 5:37 PM, Richard  Wood wrote:
>> I am sure if you go to https://www.chemaxon.com/library/, there is something that will help you there.
>>
>> Richard
>> ________________________________________
>> From: autodock-bounces at scripps.edu [autodock-bounces at scripps.edu] on behalf of sandra [sandra at theindoleshop.com]
>> Sent: Thursday, March 03, 2016 2:35 PM
>> To: autodock at scripps.edu
>> Subject: Re: ADL: Question about AutoDock tools!
>>
>> Hey thank you for this response, Richard. I was wondering if you could
>> possibly guide me towards decent tutorials on using Marvin Sketch,
>> specifically conformational distriution for a 3D model of a small ligand
>> (such as the D-isomer of ETH-LAD)? Thank you very much :) Cheers.
>>
>> On 2/25/2016 3:36 PM, Richard  Wood wrote:
>>> Actually, you could use ChemAxon's MarvinSketch to sketch molecules in 3D and save them in any format you wish.
>>> Marvin is free.
>>>
>>> Richard
>>> ________________________________________
>>> From: autodock-bounces at scripps.edu [autodock-bounces at scripps.edu] on behalf of sandra [sandra at theindoleshop.com]
>>> Sent: Wednesday, February 24, 2016 4:31 PM
>>> To: autodock at scripps.edu
>>> Subject: ADL: Question about AutoDock tools!
>>>
>>> Hi there! I am a McMaster student and I am looking to use AutoDock Tools
>>> and the Grid interface for some academic research as a student. I
>>> encountered an error while using it and I was wondering if I could
>>> possibly ask some questions. I apologize if these questions are overly
>>> lengthy or too simplistic to you as I am just a beginner.
>>>
>>> I used a model of the 5HT-1B human peptide receptor, crystallized with
>>> the ligand ergotamine. Its codename in RCSB is "41AR". I want to replace
>>> ergotamine with a different molecule, such as LSD, and dock it.
>>>
>>> I used AutoDock Tools to select the molecule ergotamine, and then delete
>>> its space. There is an empty gap left where it was docked. There is an
>>> additional molecule in the model, I believe tartaric acid. Anyways, I
>>> left the tartaric acid in because I figured LSD is also a hemi-tartrate
>>> salt, like ergotamine.
>>>
>>> Anyways, I followed this video guide on AutoDock Tools
>>> (https://www.youtube.com/watch?v=ZiuqSzqcD7M) because like my project,
>>> it is using a crystallized receptor model (not a homology-modeled one)
>>> in pdb format obtained from RCSB, is introducing a separate ligand as a
>>> PDB file, and uses Windows 8 (i am using Windows 10 for my project).
>>>
>>> I followed the steps: delete all water molecule, add all hydrogens (both
>>> polar and nonpolar), merge non-polar hydrogens, computer partial
>>> Gasteiger charges, and then I selected Input>Ligand>Select. I added in a
>>> .pdb file for LSD; I couldnt find a ligand file for LSD on the RCSB, so
>>> instead, I drew it out as a simply 2D sketch (in the d-siomer form) on
>>> ACD ChemSketch (freeware version),  saved it as a .mol file (v3000), and
>>> then I used OpenBabel to convert the v3000 .mol file into a .pdbqt file,
>>> as suggested in the tutorial vid.
>>>
>>> However when I attempted to load it, it could only partially model the
>>> ligand, and some atoms seemed to be missing. In the Python shell, there
>>> was an error message, which I have attached in this email as a .txt file.
>>>
>>> I was wondering if you would possibly be able to review over what I did
>>> and tell me where I went wrong? I understand my question is a bit ranty
>>> and rudimentary so I don't want to pressure you :P Any help however
>>> would be extraordinarily useful. Thank you very much!
>>>
>>> ________________________________________________
>>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>>>
>> ________________________________________________
>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>>
>> ________________________________________________
>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>>
>
> ------------------------------
>
> Message: 2
> Date: 6 Mar 2016 03:26:17 -0000
> From: "soumi " <soumi90 at rediffmail.com>
> Subject: ADL: Could n't open "ligand_out.pdbqt" for writing
> To: <autodock at scripps.edu>
> Message-ID: <20160306032617.25482.qmail at f4mail-235-121.rediffmail.com>
> Content-Type: text/plain
>
> -
>
>
> ------------------------------
>
> Message: 3
> Date: Sun, 6 Mar 2016 13:44:54 +0000
> From: "Richard  Wood" <Richard.Wood at purduecal.edu>
> Subject: Re: ADL: Question about AutoDock tools!
> To: "autodock at scripps.edu" <autodock at scripps.edu>
> Message-ID:
> 	<2795F52A14F49842BB6FF8003810E47D25E15CBB at PUCEX5.staff.puc.purduecal.edu>
> 	
> Content-Type: text/plain; charset="us-ascii"
>
> You could either save your MarvinSketch compound as a mol2 and convert it to a pdbqt using ADT, or or save teh MS as a pdb and convert the pdb using ADT.
>
> Richard
> ________________________________________
> From: autodock-bounces at scripps.edu [autodock-bounces at scripps.edu] on behalf of sandra [sandra at theindoleshop.com]
> Sent: Saturday, March 05, 2016 1:22 PM
> To: autodock at scripps.edu
> Subject: Re: ADL: Question about AutoDock tools!
>
> Thank you, I was able to create a .pdb file for the ligand d-ETH-LAD.
> However I did not do any conformational distribution, all I did was draw
> out the D-siomer in a 2D sketch, and converted it into a 3D .pdb file.
> When I uploaded the .pdb file into AutoDock Tools, it worked--to the
> extent that it loaded the proper 3D orientation, and it was the right
> isomerization.
>
> However, in AutoDock Tools, when i selected grid>set map ypes>choose
> ligand, and selected the ETHLAD, it says it didnt work because it only
> reads pdbqt files!
>
> MarvinSketch seems to not have any option to save in .pdbqt format. So I
> tried converting the pdb file into pdbqt using OpenBabel, a conversion
> software. However, when I tried uploading the converted pdbqt ligand
> file into AutoDock Tools (by selecting ligand>input>open), it says it
> cant read it!
>
> It seems there was a problem when converting the .pdb file to .pdbqt. Is
> there an extra step i need to do in either OpenBabel or MarvinSketch? I
> will read over the link you just sent me. Thank you so much~
>
> Best regards! :)
>
> On 3/5/2016 5:37 PM, Richard  Wood wrote:
>> I am sure if you go to https://www.chemaxon.com/library/, there is something that will help you there.
>>
>> Richard
>> ________________________________________
>> From: autodock-bounces at scripps.edu [autodock-bounces at scripps.edu] on behalf of sandra [sandra at theindoleshop.com]
>> Sent: Thursday, March 03, 2016 2:35 PM
>> To: autodock at scripps.edu
>> Subject: Re: ADL: Question about AutoDock tools!
>>
>> Hey thank you for this response, Richard. I was wondering if you could
>> possibly guide me towards decent tutorials on using Marvin Sketch,
>> specifically conformational distriution for a 3D model of a small ligand
>> (such as the D-isomer of ETH-LAD)? Thank you very much :) Cheers.
>>
>> On 2/25/2016 3:36 PM, Richard  Wood wrote:
>>> Actually, you could use ChemAxon's MarvinSketch to sketch molecules in 3D and save them in any format you wish.
>>> Marvin is free.
>>>
>>> Richard
>>> ________________________________________
>>> From: autodock-bounces at scripps.edu [autodock-bounces at scripps.edu] on behalf of sandra [sandra at theindoleshop.com]
>>> Sent: Wednesday, February 24, 2016 4:31 PM
>>> To: autodock at scripps.edu
>>> Subject: ADL: Question about AutoDock tools!
>>>
>>> Hi there! I am a McMaster student and I am looking to use AutoDock Tools
>>> and the Grid interface for some academic research as a student. I
>>> encountered an error while using it and I was wondering if I could
>>> possibly ask some questions. I apologize if these questions are overly
>>> lengthy or too simplistic to you as I am just a beginner.
>>>
>>> I used a model of the 5HT-1B human peptide receptor, crystallized with
>>> the ligand ergotamine. Its codename in RCSB is "41AR". I want to replace
>>> ergotamine with a different molecule, such as LSD, and dock it.
>>>
>>> I used AutoDock Tools to select the molecule ergotamine, and then delete
>>> its space. There is an empty gap left where it was docked. There is an
>>> additional molecule in the model, I believe tartaric acid. Anyways, I
>>> left the tartaric acid in because I figured LSD is also a hemi-tartrate
>>> salt, like ergotamine.
>>>
>>> Anyways, I followed this video guide on AutoDock Tools
>>> (https://www.youtube.com/watch?v=ZiuqSzqcD7M) because like my project,
>>> it is using a crystallized receptor model (not a homology-modeled one)
>>> in pdb format obtained from RCSB, is introducing a separate ligand as a
>>> PDB file, and uses Windows 8 (i am using Windows 10 for my project).
>>>
>>> I followed the steps: delete all water molecule, add all hydrogens (both
>>> polar and nonpolar), merge non-polar hydrogens, computer partial
>>> Gasteiger charges, and then I selected Input>Ligand>Select. I added in a
>>> .pdb file for LSD; I couldnt find a ligand file for LSD on the RCSB, so
>>> instead, I drew it out as a simply 2D sketch (in the d-siomer form) on
>>> ACD ChemSketch (freeware version),  saved it as a .mol file (v3000), and
>>> then I used OpenBabel to convert the v3000 .mol file into a .pdbqt file,
>>> as suggested in the tutorial vid.
>>>
>>> However when I attempted to load it, it could only partially model the
>>> ligand, and some atoms seemed to be missing. In the Python shell, there
>>> was an error message, which I have attached in this email as a .txt file.
>>>
>>> I was wondering if you would possibly be able to review over what I did
>>> and tell me where I went wrong? I understand my question is a bit ranty
>>> and rudimentary so I don't want to pressure you :P Any help however
>>> would be extraordinarily useful. Thank you very much!
>>>
>>> ________________________________________________
>>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>>>
>> ________________________________________________
>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>>
>> ________________________________________________
>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>>
> ________________________________________________
> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>
>
>
> ------------------------------
>
> Message: 4
> Date: Sun, 6 Mar 2016 11:00:26 -0800
> From: "Dr. Yaron Steinberg" <ymsteinberg at gmail.com>
> Subject: ADL: ADFR
> To: "autodock at scripps.edu" <autodock at scripps.edu>
> Message-ID:
> 	<CAFf7Xv_pmC6sagNdKV1AwoK36xU4B2BskzPKtHW=uTE8P3PJVw at mail.gmail.com>
> Content-Type: text/plain; charset=UTF-8
>
> Dear Prof. Sanner
>
> Why would you highlight the CDK2 result, when your overall success
> rate was 5/35 or 14%?
>
> You started with 35 systems, gave up on half of them, and for for the
> remaining 17, ADFR predicted the binding mode of 5 correctly.
>
> What are we to use a method with a 14% overall success rate for?
>
> To my mind, the most salient result of this study is that it shows
> that one can not use docking methods to model receptor movement, as
> many probably already knew.
>
> A more nuanced approach should be used instead.
>
> Ron
>
>
> On Mon, Feb 29, 2016 at 2:27 PM, Michel Sanner <sanner at scripps.edu> wrote:
>> Hello Ron
>>
>> On 2/29/16 12:50 AM, autodock-request at scripps.edu wrote:
>>> Message: 3
>>> Date: Sun, 28 Feb 2016 15:03:14 -0800
>>> From: "Dr. Yaron Steinberg"<ymsteinberg at gmail.com>
>>> Subject: Re: ADL: Software Announcement
>>> To:"autodock at scripps.edu"  <autodock at scripps.edu>
>>> Message-ID:
>>>
>>> <CAFf7Xv8FEQu5R41913pnp5J0XZfG4_jQ6wsWH0EaM7LGGVKQ5w at mail.gmail.com>
>>> Content-Type: text/plain; charset=UTF-8
>>>
>>> Interesting paper, but your reported Astex Diverse Set accuracy (74%)
>>> is actually worse than the previously published results for rDock
>>> (76%) and Vina (81%), although better than Glide's (68%).
>> I agree, however I would like to clarify that ADFR is using the AutoDock4
>> scoring function. Not surprisingly it shows identical performance to
>> AutoDock4 for this test. The points we are making in this part of the paper
>> was not about docking accuracy but rather about the higher efficiency of the
>> genetic algorithm implemented in ADFR.
>>>
>>> http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003571
>>>
>>> I am surprised by some of your conclusions though. ADFR uses 50 GA
>>> runs at 4.2 hours each, or 210 hours for each ligand. This is 1/7000th
>>> as fast as your own Vina results.
>>>
>>> When there are 12 residues, ADFR needs 430 hours for each ligand. I am
>>> surprised by your conclusion that this means that ADFR scales well. It
>>> is simply about equally slow in both cases.
>>>
>>> There must be many common components to both rigid and flexible
>>> receptor docking, including the calculation of the ligand-receptor
>>> energy and of the internal energy. The slower you make them, as ADFR
>>> seems to have done here, the longer all experiments will take, and the
>>> more equally slow everything will appear.
>> The version of ADFR described in the paper only had the C implementation of
>> the scoring function with every thing else implemented in Python, which
>> explains the lengthy run times compared to the highly optimized C++
>> implementation of Vina. The new version of ADFR that we just announced has
>> unoptimized C++ implementations of the scoring function, the flexibility
>> tree, and the local search procedure but still uses a Python implementation
>> of the genetic algorithm and clustering procedures. Yet, it  already shows a
>> 20-fold speedup over the version from the paper for the CDK2 data where we
>> dock ligands into a receptor with 12  flexible side chains.
>>
>> here are the times (in hours) for the CDK2 data set
>>
>> Python    C++    exhaus. 8   exhaus. 20  exhaus. 200
>>    ADFR     ADFR    Vina        Vina         Vina
>> 379.98    19.16   1.85        5.05          46
>>
>> As you can see new version of ADFR partly ported to C++ is currently about
>> 10 times slower than Vina with default exhaustiveness (8). however, Vina
>> becomes 2.4 times slower with exhaustiveness 200 while still not achieving
>> ADFR's success rate.
>>> In your cross-docking experiments, you say that you down-weight some
>>> terms in ADFR, but what if you simply optimized the Vina or Autodock
>>> force-fields for their best cross-docking accuracy too? Might this not
>>> be simpler and more useful than publishing a new docking program
>>> that's 1/7000th as fast as what we had before and shows worse Astex
>>> Diverse Set accuracy?
>>>
>>> What happened to the custom and unified force-fields for Vina and
>>> Autodock that were discussed in this mailing list during the last
>>> fundraising campaign? I posted many suggestions then.
>>>
>>> Ron
>>
>> best regards
>>
>> --
>>
>> -----------------------------------------------------------------------
>>     o
>>    /   Michel F. Sanner Ph.D.            The Scripps Research Institute
>> o     Associate Professor               Department of Molecular Biology
>>    \                                     10550 North Torrey Pines Road
>>     o  Tel. (858) 784-7742               La Jolla, CA 92037, TPC 26
>>    /   Fax. (858) 784-2341
>> o     sanner at scripps.edu                http://www.scripps.edu/~sanner
>> -----------------------------------------------------------------------
>>
>
> ------------------------------
>
> ________________________________________________
> --- ADL: AutoDock List  --- http://www.scripps.edu/pub/olson-web/doc/autodock/ ---
>
> End of autodock Digest, Vol 139, Issue 4
> ****************************************

-- 

-----------------------------------------------------------------------
    o
   /   Michel F. Sanner Ph.D.            The Scripps Research Institute
o     Associate Professor               Department of Molecular Biology
   \                                     10550 North Torrey Pines Road
    o  Tel. (858) 784-7742               La Jolla, CA 92037, TPC 26
   /   Fax. (858) 784-2341
o     sanner at scripps.edu                http://www.scripps.edu/~sanner
-----------------------------------------------------------------------



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