ADL: term"randomized structure"

Dinler Antunes dinler at gmail.com
Fri Mar 25 13:28:03 PDT 2016


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>:

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> Today's Topics:
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>    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


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