ADL: Heme groups

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ADL: Heme groups

Riggs, Robert
I am a very novice user of Autodock Vina and I am trying to model a ligand to a cyp enzyme.  Is there a way to do the following:

1.        Set the charge on the iron atom?  When the protein was saved as a PDQST file a flag popped up stating no charge on the iron atom.

2.       Based on the Autodock Vina tutorial and PDF file, I still do not understand how to determine the grid size for the docking.

Thanks in advance for any help.

Professor of Medicinal Chemistry & Biochemistry
McWhorter School of Pharmacy
College of Health Sciences
Samford University
800 Lakeshore Drive
Birmingham, AL 35229

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Re: ADL: Heme groups

Diogo Martins
Vina doesn't use charges, the energy terms use atom types to describe
chemical interactions. For autodock4, charges are specified in .pdbqt files
- one can edit such files with a text editor.

About the grid size, the best way is to visualize in adt / pmv or with the
autodock plugin for pymol, but I'm not sure if this is what you were asking.

On Sep 29, 2016 9:39 PM, "Riggs, Robert" <[hidden email]> wrote:

I am a very novice user of Autodock Vina and I am trying to model a ligand
to a cyp enzyme.  Is there a way to do the following:

1.        Set the charge on the iron atom?  When the protein was saved as a
PDQST file a flag popped up stating no charge on the iron atom.

2.       Based on the Autodock Vina tutorial and PDF file, I still do not
understand how to determine the grid size for the docking.

Thanks in advance for any help.

Professor of Medicinal Chemistry & Biochemistry
McWhorter School of Pharmacy
College of Health Sciences
Samford University
800 Lakeshore Drive
Birmingham, AL 35229

________________________________________________
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Re: ADL: Heme groups

Riggs, Robert
Thanks for the advice.  Question: if I do use a text editor on the .pdbqt file and specify a two-plus charge on the iron atom, will that interfere with docking algorithm?

I have zoomed in on the heme group, but not sure how to determine distance from heme group to opening to active site.  The active site is somewhat buried in the interior of the protein.

I noticed when I clicked on grid box to set the docking box a box appeared over the protein.  Is that box a rough estimate of a potential area for ligand docking?


Robert M. Riggs, Ph.D
Professor of Medicinal Chemistry and Biochemistry
McWhorter School of Pharmacy

205-726-2097<tel:205-726-2097> | office
205-726-2088<tel:205-726-2088> | fax
[hidden email]<mailto:[hidden email]>
www.samford.edu/pharmacy<http://www.samford.edu/pharmacy>
800 Lakeshore Drive, Birmingham, AL 35229<http://maps.google.com/maps?q=800+Lakeshore+Drive,+Birmingham,+AL+35229,+US>


On Sep 29, 2016, at 15:54, Diogo Martins <[hidden email]<mailto:[hidden email]>> wrote:

Vina doesn't use charges, the energy terms use atom types to describe
chemical interactions. For autodock4, charges are specified in .pdbqt files
- one can edit such files with a text editor.

About the grid size, the best way is to visualize in adt / pmv or with the
autodock plugin for pymol, but I'm not sure if this is what you were asking.

On Sep 29, 2016 9:39 PM, "Riggs, Robert" <[hidden email]<mailto:[hidden email]>> wrote:

I am a very novice user of Autodock Vina and I am trying to model a ligand
to a cyp enzyme.  Is there a way to do the following:

1.        Set the charge on the iron atom?  When the protein was saved as a
PDQST file a flag popped up stating no charge on the iron atom.

2.       Based on the Autodock Vina tutorial and PDF file, I still do not
understand how to determine the grid size for the docking.

Thanks in advance for any help.

Professor of Medicinal Chemistry & Biochemistry
McWhorter School of Pharmacy
College of Health Sciences
Samford University
800 Lakeshore Drive
Birmingham, AL 35229

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Re: ADL: Heme groups

Ghebremedhin, Anghesom
In reply to this post by Diogo Martins
Dear Sir/Madam,

Good evening. I wanted to generate a real time video for the interactions
of my ligand and receptors. Is it possible to do it in ADV? If not can you
suggest me how I can perform this task. Looking forward to hearing from you
and thanks a lot in advance for your cooperation.

Thanks,
Anghesom

On Thu, Sep 29, 2016 at 3:50 PM, Diogo Martins <[hidden email]>
wrote:

> Vina doesn't use charges, the energy terms use atom types to describe
> chemical interactions. For autodock4, charges are specified in .pdbqt files
> - one can edit such files with a text editor.
>
> About the grid size, the best way is to visualize in adt / pmv or with the
> autodock plugin for pymol, but I'm not sure if this is what you were
> asking.
>
> On Sep 29, 2016 9:39 PM, "Riggs, Robert" <[hidden email]> wrote:
>
> I am a very novice user of Autodock Vina and I am trying to model a ligand
> to a cyp enzyme.  Is there a way to do the following:
>
> 1.        Set the charge on the iron atom?  When the protein was saved as a
> PDQST file a flag popped up stating no charge on the iron atom.
>
> 2.       Based on the Autodock Vina tutorial and PDF file, I still do not
> understand how to determine the grid size for the docking.
>
> Thanks in advance for any help.
>
> Professor of Medicinal Chemistry & Biochemistry
> McWhorter School of Pharmacy
> College of Health Sciences
> Samford University
> 800 Lakeshore Drive
> Birmingham, AL 35229
>
> ________________________________________________
> --- 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 ---
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Re: ADL: Heme groups

Diogo Martins
In reply to this post by Riggs, Robert
In short:
Yes, AutoDock4 results depend on the charge in Fe - both binding poses and
energies. AutoDock Vina ignores charges.
No, the initial box is not an estimate of search space.

Your questions deserve a longer answer; the best is take a look in the
following materials as they've been written to cover these and other
topics:
* http://vina.scripps.edu (tutorial, manual, FAQ)
*
http://autodock.scripps.edu/faqs-help/manual/autodock-4-2-user-guide/AutoDock4.2.6_UserGuide.pdf
* http://autodock.scripps.edu/faqs-help/faq


On 30 September 2016 at 01:23, Riggs, Robert <[hidden email]> wrote:

> Thanks for the advice.  Question: if I do use a text editor on the .pdbqt
> file and specify a two-plus charge on the iron atom, will that interfere
> with docking algorithm?


> I have zoomed in on the heme group, but not sure how to determine distance
> from heme group to opening to active site.  The active site is somewhat
> buried in the interior of the protein.
>
> I noticed when I clicked on grid box to set the docking box a box appeared
> over the protein.  Is that box a rough estimate of a potential area for
> ligand docking?
>
>
> Robert M. Riggs, Ph.D
> Professor of Medicinal Chemistry and Biochemistry
> McWhorter School of Pharmacy
>
> 205-726-2097<tel:205-726-2097> | office
> 205-726-2088<tel:205-726-2088> | fax
> [hidden email]<mailto:[hidden email]>
> www.samford.edu/pharmacy<http://www.samford.edu/pharmacy>
> 800 Lakeshore Drive, Birmingham, AL 35229<http://maps.google.com/m
> aps?q=800+Lakeshore+Drive,+Birmingham,+AL+35229,+US>
>
>
> On Sep 29, 2016, at 15:54, Diogo Martins <[hidden email]<mailto:
> [hidden email]>> wrote:
>
> Vina doesn't use charges, the energy terms use atom types to describe
> chemical interactions. For autodock4, charges are specified in .pdbqt files
> - one can edit such files with a text editor.
>
> About the grid size, the best way is to visualize in adt / pmv or with the
> autodock plugin for pymol, but I'm not sure if this is what you were
> asking.
>
> On Sep 29, 2016 9:39 PM, "Riggs, Robert" <[hidden email]<mailto:rm
> [hidden email]>> wrote:
>
> I am a very novice user of Autodock Vina and I am trying to model a ligand
> to a cyp enzyme.  Is there a way to do the following:
>
> 1.        Set the charge on the iron atom?  When the protein was saved as a
> PDQST file a flag popped up stating no charge on the iron atom.
>
> 2.       Based on the Autodock Vina tutorial and PDF file, I still do not
> understand how to determine the grid size for the docking.
>
> Thanks in advance for any help.
>
> Professor of Medicinal Chemistry & Biochemistry
> McWhorter School of Pharmacy
> College of Health Sciences
> Samford University
> 800 Lakeshore Drive
> Birmingham, AL 35229
>
> ________________________________________________
> --- ADL: AutoDock List  --- https://urldefense.proofpoint.
> com/v2/url?u=http-3A__autodock.scripps.edu_mailing-5Flist&d=
> DQICAg&c=GTxgfYI6i4KYikqC6GK_Jzn2mYGEh-v4HEPYCyQcJzU&r=
> J7Ip0g3Ta_TgeFn0CwHnOvfE-3ndVPuXr_e-XJ8CAag&m=hsch7-
> 9gI0w_rJL7iaNODU-0Gj7vtI2M1iy70TukikQ&s=92bn0EacNMth5X39LJy4
> C-Yn5Nws_jedNd4Gm9J01M4&e=  ---
> ________________________________________________
> --- ADL: AutoDock List  --- https://urldefense.proofpoint.
> com/v2/url?u=http-3A__autodock.scripps.edu_mailing-5Flist&d=
> DQICAg&c=GTxgfYI6i4KYikqC6GK_Jzn2mYGEh-v4HEPYCyQcJzU&r=
> J7Ip0g3Ta_TgeFn0CwHnOvfE-3ndVPuXr_e-XJ8CAag&m=hsch7-
> 9gI0w_rJL7iaNODU-0Gj7vtI2M1iy70TukikQ&s=92bn0EacNMth5X39LJy4
> C-Yn5Nws_jedNd4Gm9J01M4&e=  ---
> ________________________________________________
> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>
________________________________________________
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Re: ADL: Heme groups

dr. sakura
Hello Diogo,

Since I've read your message I doubt if Autodock Vina doesn't recognize metals in a ligand molecule or doesn't differentiate whether, let's say, it's a Zn or Ni atom.

I ask this because I dock a ligand to DNA only changing the metal in the center.

Thank you very much in advance.
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Re: ADL: Heme groups

Diogo Martins
Hi,

Autodock Vina is based on X-Score, here's a relevant quote from the X-Score
paper:
http://sw16.im.med.umich.edu/software/xtool/manual/xscore.pdf

"Note that technically we define metal ions as ‘donor’ so that the
metal-ligand coordinated bonds are calculated with exactly the same
distance and angular functions of hydrogen bonding."


On 2 October 2016 at 18:52, dr. sakura <[hidden email]> wrote:

> Hello Diogo,
>
> Since I've read your message I doubt if Autodock Vina doesn't recognize
> metals in a ligand molecule or doesn't differentiate whether, let's say,
> it's a Zn or Ni atom.
>
> I ask this because I dock a ligand to DNA only changing the metal in the
> center.
>
> Thank you very much in advance.
>
>
>
> --
> View this message in context: http://autodock.1369657.n2.
> nabble.com/ADL-Heme-groups-tp7579604p7579609.html
> Sent from the AutoDock mailing list archive at Nabble.com.
> ________________________________________________
> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>
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Re: ADL: Heme groups

dr. sakura
Hello again Diogo,

Thanks for this valuable information but it is still not completely clear to me. When I docked ZnPc, NiPc, CuPc, FePc using Vina, I obtained the same binding energy for each (for the best binding conformer).  Do you think this result is realistic? Or, is Vina not accurate enough in comparing the effects of metals in organometallic ligands because of XCSCORE scoring function.

Thank you!
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Re: ADL: Heme groups

Diogo Martins
Hi,

What you wrote is correct: Vina can't distinguish metals from each other
because all metals are treated in the same way - as a hydrogen bond donor
atom.

All the best,

On Oct 5, 2016 7:35 AM, "dr. sakura" <[hidden email]> wrote:

> Hello again Diogo,
>
> Thanks for this valuable information but it is still not completely clear
> to
> me. When I docked ZnPc, NiPc, CuPc, FePc using Vina, I obtained the same
> binding energy for each (for the best binding conformer).  Do you think
> this
> result is realistic? Or, is Vina not accurate enough in comparing the
> effects of metals in organometallic ligands because of XCSCORE scoring
> function.
>
> Thank you!
>
>
>
> --
> View this message in context: http://autodock.1369657.n2.nab
> ble.com/ADL-Heme-groups-tp7579604p7579615.html
> Sent from the AutoDock mailing list archive at Nabble.com.
> ________________________________________________
> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>
________________________________________________
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Re: ADL: Heme groups

dr. sakura
Well, that was deadly important to me. Thank you so much Diogo.
I also ran Autodock 4 dockings. What would you say for its scoring function, regarding recognizing metals?
This will be the last, I promise.
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Re: ADL: Heme groups

Diogo Martins
This information is important yet hard to find, it's a good thing to bring
up these questions.

Autodock4 uses vdW potentials with different well depths and radius for
different metals. Furthermore, charges can be changed manually. So you'll
get different energies.

vdW potentials + atomic partial charges are certainly unable to describe
all relevant electronic effects for all metals. For example, spin states
and charge transfer are definitely beyond a forcefield description. I'd
recommend doing a literature check on how well (or how bad) forcefields
describe the specific metals you are interested in.

On Oct 7, 2016 10:37 AM, "dr. sakura" <[hidden email]> wrote:

> Well, that was deadly important to me. Thank you so much Diogo.
> I also ran Autodock 4 dockings. What would you say for its scoring
> function,
> regarding recognizing metals?
> This will be the last, I promise.
>
>
>
> --
> View this message in context: http://autodock.1369657.n2.nab
> ble.com/ADL-Heme-groups-tp7579604p7579618.html
> Sent from the AutoDock mailing list archive at Nabble.com.
> ________________________________________________
> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>
________________________________________________
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Re: ADL: Heme groups

Alcides Simão
 

Regarding Diogo's recommendation, I've came across an article by a
couple of Cornell University scientists entitled "Simple Molecular
Reactive Force Field for Metal-Organic Synthesis". While at first it
seems to be a bit off-topic, it does have a considerable amount of
interesting information that is directly appliable to this
subject.

DOI:10.1021/acs.jctc.5b00918

Cheers!
Em 2016-10-07 17:07,
Diogo Martins escreveu:

> This information is important yet hard to
find, it's a good thing to bring
> up these questions.
>
> Autodock4
uses vdW potentials with different well depths and radius for
>
different metals. Furthermore, charges can be changed manually. So
you'll
> get different energies.
>
> vdW potentials + atomic partial
charges are certainly unable to describe
> all relevant electronic
effects for all metals. For example, spin states
> and charge transfer
are definitely beyond a forcefield description. I'd
> recommend doing a
literature check on how well (or how bad) forcefields
> describe the
specific metals you are interested in.
>
> On Oct 7, 2016 10:37 AM,
"dr. sakura" <[hidden email]> wrote:
>
>> Well, that was
deadly important to me. Thank you so much Diogo. I also ran Autodock 4
dockings. What would you say for its scoring function, regarding
recognizing metals? This will be the last, I promise. -- View this
message in context: http://autodock.1369657.n2.nab [1]
ble.com/ADL-Heme-groups-tp7579604p7579618.html Sent from the AutoDock
mailing list archive at Nabble.com.
________________________________________________ --- ADL: AutoDock List
--- http://autodock.scripps.edu/mailing_list [2] ---
>
>
________________________________________________
> --- ADL: AutoDock
List --- http://autodock.scripps.edu/mailing_list [2] ---

--

Alcides
Simão, AMRSC / M. Sc., PhD Student /

[hidden email]

University
of Coimbra Office: +351 239 852 080
/ Fax: +351 239 827 703

Departamento de Química da Universidade de Coimbra, 3004-535 COIMBRA,
PORTUGAL
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Re: ADL: Heme groups

dr. sakura
In reply to this post by Diogo Martins
Thank you so much again, Diogo. I truly appreciate your help.

All the best,
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Re: ADL: Heme groups

dr. sakura
In reply to this post by Alcides Simão
I downloaded and read the article, however couldn't recognize any valuable knowledge relevant to this issue. Or I'm not knowledgable enough to realize any. In either way, thank you for the support, Alcides!