ADL: term"randomized structure"

Debojit Bhattacherjee debu.yaman at gmail.com
Fri Mar 25 20:28:34 PDT 2016


Dear all,
I have managed to incorporate the additional force field parameters of some
atoms  in autodock 4.2. Please can you tell me the source where i can get
the actual parameter values of se, Te, Au, Ru, etc. Kindly help me out. I
am waiting for your reply. Thank you

On Sat, Mar 26, 2016 at 2:33 AM, Stefano Forli <forli at scripps.edu> wrote:

> This topic is very important, and I believe it's great that such issues
> are discussed in the community.
>
> Ideally, you would be right: if a program could perform efficient searches
> and unbiased internal randomizations, there would be no need for
> pre-randomizing the input externally.
>
> Although, very likely this is not the case.
> First, any conformational sampling which is not perfect will be limited by
> the starting point, even when generating the internal randomized starting
> point.
> That's why, explicitly or under the hood, all docking programs run
> multiple independent searches.
>
> Cases have been reported where the re-docking success rate was higher when
> starting from the experimental coordinates, even when only the geometric
> center of the input was overlapping with the solution.
>
> Also, if for some reason (incorrect implementation, rounding errors, etc.)
> there is a bias toward toward zero values, if the internally randomized
> conformations are generated by deviating from the input state, the search
> will drift toward the input.
>
> That said, randomizing the input is not a requirement for re-dockings, but
> it's definitely a good choice to simulate real-life conditions.
> Crystal structures represent the ligand conformations minimized to fit the
> density maps, which depend on experimental parameters, conditions, etc.,
> and can result in distorted geometries.
> Ligand libraries used in virtual screening, on the other hand, have ideal
> coordinates, so could not be able to match experimental coordinates.
> Testing a the re-docking of the crystallographic ligand using ideal
> coordinates generated externally can allow you to assess the chances of
> success of your dockings.
>
> There are many papers on these two topics, but these are an excellent
> start:
> http://onlinelibrary.wiley.com/doi/10.1002/prot.20497/full
> http://pubs.acs.org/doi/abs/10.1021/jm8016464
>
> Happy dockings,
>
> S
>
>
>
> On 03/25/2016 01:28 PM, Dinler Antunes wrote:
>
>> Following up on this discussion on the randomized initial structure, this
>> is not a requirement for redocking, right? I mean, regardless of the input
>> 3D conformation of the ligand both Autodock4 and Vina will start the
>> ligand
>> using a random seed. This will be used to randomize the initial
>> conformation, right? Or it will only be used to randomize rotational and
>> translational degrees of freedom?
>>
>> BW,
>>
>> Dinler Antunes
>>
>>
>> 2016-03-25 13:42 GMT-05:00 <autodock-request at scripps.edu>:
>>
>> Send autodock mailing list submissions to
>>>          autodock at scripps.edu
>>>
>>> To subscribe or unsubscribe via the World Wide Web, visit
>>>          http://mgldev.scripps.edu/mailman/listinfo/autodock
>>> or, via email, send a message with subject or body 'help' to
>>>          autodock-request at scripps.edu
>>>
>>> You can reach the person managing the list at
>>>          autodock-owner at scripps.edu
>>>
>>> When replying, please edit your Subject line so it is more specific
>>> than "Re: Contents of autodock digest..."
>>>
>>>
>>> Today's Topics:
>>>
>>>     1.  term"randomized structure" (maria timoshik)
>>>     2. Re:  term"randomized structure" (Richard  Wood)
>>>     3. Re:  term"randomized structure" (Stefano Forli)
>>>     4. Re:  term"randomized structure" (Richard  Wood)
>>>     5.  Question about Autodock Vina counter ions (Tye Martin)
>>>     6. Re:  term"randomized structure" (Stefano Forli)
>>>
>>>
>>> ----------------------------------------------------------------------
>>>
>>> Message: 1
>>> Date: Thu, 24 Mar 2016 22:30:23 +0300
>>> From: maria timoshik <m.timoshik at yandex.ru>
>>> Subject: ADL: term"randomized structure"
>>> To: "autodock at scripps.edu" <autodock at scripps.edu>
>>> Message-ID: <796051458847823 at web20h.yandex.ru>
>>> Content-Type: text/plain
>>>
>>> Hello:
>>> I've heard that in a very beginning of video tutorial to Vina Dr. Oleg
>>> Todd said:
>>> "I'll use a randomized structure of a drug molecule".
>>> What the term RANDOMIZED STRUCTURE actually mean in this context?
>>> Perhaps professional physico-chemists can explain?
>>>
>>> with regards, Maria
>>>
>>>
>>> ------------------------------
>>>
>>> Message: 2
>>> Date: Fri, 25 Mar 2016 01:09:32 +0000
>>> From: "Richard  Wood" <Richard.Wood at purduecal.edu>
>>> Subject: Re: ADL: term"randomized structure"
>>> To: "autodock at scripps.edu" <autodock at scripps.edu>
>>> Message-ID:
>>>          <
>>> 2795F52A14F49842BB6FF8003810E47D25E1D21A at PUCEX5.staff.puc.purduecal.edu>
>>>
>>> Content-Type: text/plain; charset="us-ascii"
>>>
>>> Non-optimized?
>>>
>>> Richard
>>>
>>> ________________________________________
>>> From: autodock-bounces at scripps.edu [autodock-bounces at scripps.edu] on
>>> behalf of maria timoshik [m.timoshik at yandex.ru]
>>> Sent: Thursday, March 24, 2016 2:30 PM
>>> To: autodock at scripps.edu
>>> Subject: ADL: term"randomized structure"
>>>
>>> Hello:
>>> I've heard that in a very beginning of video tutorial to Vina Dr. Oleg
>>> Todd said:
>>> "I'll use a randomized structure of a drug molecule".
>>> What the term RANDOMIZED STRUCTURE actually mean in this context?
>>> Perhaps professional physico-chemists can explain?
>>>
>>> with regards, Maria
>>> ________________________________________________
>>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>>>
>>>
>>>
>>> ------------------------------
>>>
>>> Message: 3
>>> Date: Thu, 24 Mar 2016 18:17:44 -0700
>>> From: Stefano Forli <forli at scripps.edu>
>>> Subject: Re: ADL: term"randomized structure"
>>> To: "autodock at scripps.edu" <autodock at scripps.edu>
>>> Message-ID: <56F491B8.5000905 at scripps.edu>
>>> Content-Type: text/plain; charset="windows-1252"; format=flowed
>>>
>>> Hi,
>>> a general practice when testing docking programs is to prevent any kind
>>> of
>>> bias in the
>>> input structures that can simplify the search and artificially increase
>>> re-docking success
>>> rate.
>>>
>>> For this reason, the input structures should be randomized to be
>>> different
>>> from the
>>> solution, but still optimized, i.e., all bond angles and lengths must be
>>> correct.
>>>
>>> The ideal approach would be to generate the 3D coordinates of the ligand
>>> starting from
>>> scratch (e.g., SMILES format) using an external software and dock that.
>>>
>>> Although, since during docking bond angles and lengths are not altered,
>>> it
>>> is sufficient
>>> to randomize the conformation of the ligand from its experimental
>>> coordinates in a
>>> crystallographic complex, by altering its position, orientation and all
>>> the angles in
>>> rotatable bonds.
>>>
>>>
>>> S
>>>
>>>
>>>
>>> On 03/24/2016 06:09 PM, Richard  Wood wrote:
>>>
>>>> Non-optimized?
>>>>
>>>> Richard
>>>>
>>>> ________________________________________
>>>> From: autodock-bounces at scripps.edu [autodock-bounces at scripps.edu] on
>>>>
>>> behalf of maria timoshik [m.timoshik at yandex.ru]
>>>
>>>> Sent: Thursday, March 24, 2016 2:30 PM
>>>> To: autodock at scripps.edu
>>>> Subject: ADL: term"randomized structure"
>>>>
>>>> Hello:
>>>> I've heard that in a very beginning of video tutorial to Vina Dr. Oleg
>>>>
>>> Todd said:
>>>
>>>> "I'll use a randomized structure of a drug molecule".
>>>> What the term RANDOMIZED STRUCTURE actually mean in this context?
>>>> Perhaps professional physico-chemists can explain?
>>>>
>>>> with regards, Maria
>>>> ________________________________________________
>>>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list
>>>> ---
>>>>
>>>> ________________________________________________
>>>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list
>>>> ---
>>>>
>>>>
>>> --
>>>
>>>    Stefano Forli, PhD
>>>
>>>    Assistant Professor of Integrative
>>>    Structural and Computational Biology,
>>>    Molecular Graphics Laboratory
>>>
>>>    Dept. of Integrative Structural
>>>     and Computational Biology, MB-112A
>>>    The Scripps Research Institute
>>>    10550  North Torrey Pines Road
>>>    La Jolla,  CA 92037-1000,  USA.
>>>
>>>       tel: +1 (858)784-2055
>>>       fax: +1 (858)784-2860
>>>       email: forli at scripps.edu
>>>       http://www.scripps.edu/~forli/
>>>
>>>
>>> ------------------------------
>>>
>>> Message: 4
>>> Date: Fri, 25 Mar 2016 13:03:07 +0000
>>> From: "Richard  Wood" <Richard.Wood at purduecal.edu>
>>> Subject: Re: ADL: term"randomized structure"
>>> To: "autodock at scripps.edu" <autodock at scripps.edu>
>>> Message-ID:
>>>          <
>>> 2795F52A14F49842BB6FF8003810E47D25E1D243 at PUCEX5.staff.puc.purduecal.edu>
>>>
>>> Content-Type: text/plain; charset="us-ascii"
>>>
>>> Generally, unless one uses a 2-D drawing program, most sketching programs
>>> will do some kind of "quick and dirty" optimization.  So, when I said,
>>> "non-optimized", that is what I was referring to.  Of course, one can
>>> also
>>> do a full blown optimization and dock that as well.
>>>
>>> It is probably best to remove the ligand from a ligand-protein crystal
>>> structure and re-dock the ligand to see if one can place it in its
>>> correct
>>> position.  One can then tweak docking parameters to see if they can
>>> reproduce the crystal ligand pose.  You can then calculate the RMSD
>>> between
>>> your docked ligand and that of the crystal structure ligand.  If one is
>>> careful, you can get an RMSD of less than 0.5.  (As an aside, I was at an
>>> ACS talk a few years back, and there was a speaker from some pharma
>>> company
>>> who was re-docking ligands and comparing them to the crystal.  He was
>>> proud
>>> of the fact that his RMSDs were less than 2.  I told him after his talk
>>> that he could do much better than that (he I was a lowly post-doc and he
>>> was a "professional modeler"-I still remain far below "professional
>>> modeler").)
>>>
>>> It's questionable how many people actually do that, however.
>>>
>>> Richard
>>> ________________________________________
>>> From: autodock-bounces at scripps.edu [autodock-bounces at scripps.edu] on
>>> behalf of Stefano Forli [forli at scripps.edu]
>>> Sent: Thursday, March 24, 2016 8:17 PM
>>> To: autodock at scripps.edu
>>> Subject: Re: ADL: term"randomized structure"
>>>
>>> Hi,
>>> a general practice when testing docking programs is to prevent any kind
>>> of
>>> bias in the
>>> input structures that can simplify the search and artificially increase
>>> re-docking success
>>> rate.
>>>
>>> For this reason, the input structures should be randomized to be
>>> different
>>> from the
>>> solution, but still optimized, i.e., all bond angles and lengths must be
>>> correct.
>>>
>>> The ideal approach would be to generate the 3D coordinates of the ligand
>>> starting from
>>> scratch (e.g., SMILES format) using an external software and dock that.
>>>
>>> Although, since during docking bond angles and lengths are not altered,
>>> it
>>> is sufficient
>>> to randomize the conformation of the ligand from its experimental
>>> coordinates in a
>>> crystallographic complex, by altering its position, orientation and all
>>> the angles in
>>> rotatable bonds.
>>>
>>>
>>> S
>>>
>>>
>>>
>>> On 03/24/2016 06:09 PM, Richard  Wood wrote:
>>>
>>>> Non-optimized?
>>>>
>>>> Richard
>>>>
>>>> ________________________________________
>>>> From: autodock-bounces at scripps.edu [autodock-bounces at scripps.edu] on
>>>>
>>> behalf of maria timoshik [m.timoshik at yandex.ru]
>>>
>>>> Sent: Thursday, March 24, 2016 2:30 PM
>>>> To: autodock at scripps.edu
>>>> Subject: ADL: term"randomized structure"
>>>>
>>>> Hello:
>>>> I've heard that in a very beginning of video tutorial to Vina Dr. Oleg
>>>>
>>> Todd said:
>>>
>>>> "I'll use a randomized structure of a drug molecule".
>>>> What the term RANDOMIZED STRUCTURE actually mean in this context?
>>>> Perhaps professional physico-chemists can explain?
>>>>
>>>> with regards, Maria
>>>> ________________________________________________
>>>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list
>>>> ---
>>>>
>>>> ________________________________________________
>>>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list
>>>> ---
>>>>
>>>>
>>> --
>>>
>>>    Stefano Forli, PhD
>>>
>>>    Assistant Professor of Integrative
>>>    Structural and Computational Biology,
>>>    Molecular Graphics Laboratory
>>>
>>>    Dept. of Integrative Structural
>>>     and Computational Biology, MB-112A
>>>    The Scripps Research Institute
>>>    10550  North Torrey Pines Road
>>>    La Jolla,  CA 92037-1000,  USA.
>>>
>>>       tel: +1 (858)784-2055
>>>       fax: +1 (858)784-2860
>>>       email: forli at scripps.edu
>>>       http://www.scripps.edu/~forli/
>>> ________________________________________________
>>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>>>
>>>
>>>
>>> ------------------------------
>>>
>>> Message: 5
>>> Date: Fri, 25 Mar 2016 17:09:15 +0000
>>> From: Tye Martin <tmarti16 at unm.edu>
>>> Subject: ADL: Question about Autodock Vina counter ions
>>> To: "autodock at scripps.edu" <autodock at scripps.edu>
>>> Message-ID:
>>>          <
>>>
>>> CY1PR0701MB1678C3DE890B83A89BC57207C6830 at CY1PR0701MB1678.namprd07.prod.outlook.com
>>>
>>>>
>>>>
>>> Content-Type: text/plain; charset="iso-8859-1"
>>>
>>> Hello,
>>>
>>> I was wondering if Vina uses any kind of counter ions during the
>>> simulation process? I study charged ligand-protein systems and use
>>> counter
>>> ions during molecular dynamics simulations, so I was just curious if
>>> docking does something similar by default.
>>>
>>> Thank you.
>>>
>>>
>>>
>>> ------------------------------
>>>
>>> Message: 6
>>> Date: Fri, 25 Mar 2016 11:42:51 -0700
>>> From: Stefano Forli <forli at scripps.edu>
>>> Subject: Re: ADL: term"randomized structure"
>>> To: "autodock at scripps.edu" <autodock at scripps.edu>
>>> Message-ID: <56F586AB.5050307 at scripps.edu>
>>> Content-Type: text/plain; charset="windows-1252"; format=flowed
>>>
>>> Hi Richard,
>>> just to clarify, if you create your molecule from scratch (e.g., you
>>> sketch it from a 2D
>>> programs like ChemDraw) you want to carefully prepare the 3D coordinates,
>>> so you *must* do
>>> a complete minimization.
>>>
>>> In fact, pretty much every docking software (including AutoDock) do not
>>> alter bond angles
>>> and lengths during the calculation, so if your structure is distorted or
>>> not optimal, it
>>> will lead to poor/wrong results.
>>> Several papers showed redocking ligand structures generated from SMILES
>>> can reduce docking
>>> accuracy by >20%.
>>>
>>> About the RMSD cutoff, 2.0 A is widely accepted as the standard for
>>> evaluating docking
>>> performance, even though there's strong agreement on RMSD itself being a
>>> poor metric for
>>> docking accuracy.
>>> Alternatives get constantly proposed, but despite its limitations, within
>>> 2.0 A range you
>>> can assume that most of the known essential interactions with the target
>>> have been
>>> established.
>>>
>>> Best,
>>>
>>> S
>>>
>>> On 03/25/2016 06:03 AM, Richard  Wood wrote:
>>>
>>>> Generally, unless one uses a 2-D drawing program, most sketching
>>>>
>>> programs will do some kind of "quick and dirty" optimization.  So, when I
>>> said, "non-optimized", that is what I was referring to.  Of course, one
>>> can
>>> also do a full blown optimization and dock that as well.
>>>
>>>>
>>>> It is probably best to remove the ligand from a ligand-protein crystal
>>>>
>>> structure and re-dock the ligand to see if one can place it in its
>>> correct
>>> position.  One can then tweak docking parameters to see if they can
>>> reproduce the crystal ligand pose.  You can then calculate the RMSD
>>> between
>>> your docked ligand and that of the crystal structure ligand.  If one is
>>> careful, you can get an RMSD of less than 0.5.  (As an aside, I was at an
>>> ACS talk a few years back, and there was a speaker from some pharma
>>> company
>>> who was re-docking ligands and comparing them to the crystal.  He was
>>> proud
>>> of the fact that his RMSDs were less than 2.  I told him after his talk
>>> that he could do much better than that (he I was a lowly post-doc and he
>>> was a "professional modeler"-I still remain far below "professional
>>> modeler").)
>>>
>>>>
>>>> It's questionable how many people actually do that, however.
>>>>
>>>> Richard
>>>> ________________________________________
>>>> From: autodock-bounces at scripps.edu [autodock-bounces at scripps.edu] on
>>>>
>>> behalf of Stefano Forli [forli at scripps.edu]
>>>
>>>> Sent: Thursday, March 24, 2016 8:17 PM
>>>> To: autodock at scripps.edu
>>>> Subject: Re: ADL: term"randomized structure"
>>>>
>>>> Hi,
>>>> a general practice when testing docking programs is to prevent any kind
>>>>
>>> of bias in the
>>>
>>>> input structures that can simplify the search and artificially increase
>>>>
>>> re-docking success
>>>
>>>> rate.
>>>>
>>>> For this reason, the input structures should be randomized to be
>>>>
>>> different from the
>>>
>>>> solution, but still optimized, i.e., all bond angles and lengths must be
>>>>
>>> correct.
>>>
>>>>
>>>> The ideal approach would be to generate the 3D coordinates of the ligand
>>>>
>>> starting from
>>>
>>>> scratch (e.g., SMILES format) using an external software and dock that.
>>>>
>>>> Although, since during docking bond angles and lengths are not altered,
>>>>
>>> it is sufficient
>>>
>>>> to randomize the conformation of the ligand from its experimental
>>>>
>>> coordinates in a
>>>
>>>> crystallographic complex, by altering its position, orientation and all
>>>>
>>> the angles in
>>>
>>>> rotatable bonds.
>>>>
>>>>
>>>> S
>>>>
>>>>
>>>>
>>>> On 03/24/2016 06:09 PM, Richard  Wood wrote:
>>>>
>>>>> Non-optimized?
>>>>>
>>>>> Richard
>>>>>
>>>>> ________________________________________
>>>>> From: autodock-bounces at scripps.edu [autodock-bounces at scripps.edu] on
>>>>>
>>>> behalf of maria timoshik [m.timoshik at yandex.ru]
>>>
>>>> Sent: Thursday, March 24, 2016 2:30 PM
>>>>> To: autodock at scripps.edu
>>>>> Subject: ADL: term"randomized structure"
>>>>>
>>>>> Hello:
>>>>> I've heard that in a very beginning of video tutorial to Vina Dr. Oleg
>>>>>
>>>> Todd said:
>>>
>>>> "I'll use a randomized structure of a drug molecule".
>>>>> What the term RANDOMIZED STRUCTURE actually mean in this context?
>>>>> Perhaps professional physico-chemists can explain?
>>>>>
>>>>> with regards, Maria
>>>>> ________________________________________________
>>>>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list
>>>>>
>>>> ---
>>>
>>>>
>>>>> ________________________________________________
>>>>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list
>>>>>
>>>> ---
>>>
>>>>
>>>>>
>>>> --
>>>>
>>>>     Stefano Forli, PhD
>>>>
>>>>     Assistant Professor of Integrative
>>>>     Structural and Computational Biology,
>>>>     Molecular Graphics Laboratory
>>>>
>>>>     Dept. of Integrative Structural
>>>>      and Computational Biology, MB-112A
>>>>     The Scripps Research Institute
>>>>     10550  North Torrey Pines Road
>>>>     La Jolla,  CA 92037-1000,  USA.
>>>>
>>>>        tel: +1 (858)784-2055
>>>>        fax: +1 (858)784-2860
>>>>        email: forli at scripps.edu
>>>>        http://www.scripps.edu/~forli/
>>>> ________________________________________________
>>>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list
>>>> ---
>>>>
>>>> ________________________________________________
>>>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list
>>>> ---
>>>>
>>>>
>>> --
>>>
>>>    Stefano Forli, PhD
>>>
>>>    Assistant Professor of Integrative
>>>    Structural and Computational Biology,
>>>    Molecular Graphics Laboratory
>>>
>>>    Dept. of Integrative Structural
>>>     and Computational Biology, MB-112A
>>>    The Scripps Research Institute
>>>    10550  North Torrey Pines Road
>>>    La Jolla,  CA 92037-1000,  USA.
>>>
>>>       tel: +1 (858)784-2055
>>>       fax: +1 (858)784-2860
>>>       email: forli at scripps.edu
>>>       http://www.scripps.edu/~forli/
>>>
>>>
>>> ------------------------------
>>>
>>> ________________________________________________
>>> --- ADL: AutoDock List  ---
>>> http://www.scripps.edu/pub/olson-web/doc/autodock/ ---
>>>
>>> End of autodock Digest, Vol 139, Issue 14
>>> *****************************************
>>>
>>>
>>
>>
>> --
>> Dinler Amaral Antunes
>> ________________________________________________
>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>>
>>
> --
>
>  Stefano Forli, PhD
>
>  Assistant Professor of Integrative
>  Structural and Computational Biology,
>  Molecular Graphics Laboratory
>
>  Dept. of Integrative Structural
>   and Computational Biology, MB-112A
>  The Scripps Research Institute
>  10550  North Torrey Pines Road
>  La Jolla,  CA 92037-1000,  USA.
>
>     tel: +1 (858)784-2055
>     fax: +1 (858)784-2860
>     email: forli at scripps.edu
>     http://www.scripps.edu/~forli/
> ________________________________________________
> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>



-- 
*Debojit Bhattacherjee*
*M.PHARM (Pharmaceutical Chemistry)*
*7/5/B/1, Nabin Chandra Das Road,*
*Kolkata-700090*


More information about the autodock mailing list