Dock heme to P450, then re-use best structure to dock ligand

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Dock heme to P450, then re-use best structure to dock ligand

AVanheule
Hi everyone,

I have a P450 monooxygenase that I would like to use in docking. The structure that I have does not include the heme group. I have carried out two seperate dockings: I docked my heme group to my receptor, and I docked my ligand to my receptor. Unfortunately, when I combine those results they don't really make a lot of sense. They are perfectly in the same active site cavity, but there are minor overlaps. I figure that I should find a way to include the ideal docked state of my heme group (reassuringly, the differences between the different heme conformations are minimal, and literature suggests that this docking is correct) in my receptor structure, THEN use that new structure to dock my ligand.

I have been able to combine my receptor structure and my best heme docking in one pdb file without problems, but the trouble starts when I read that pdb file in AutodockTools to create my new .pdbqt file for the second round of docking (with the ligand). Is this not the correct approach? How should I go about this?

Thank you for any help,
Kind regards
Adriaan
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Re: ADL: Dock heme to P450, then re-use best structure to dock ligand

Oleg Trott
Hi

You probably want to dock the cofactor first, merge it with the
receptor to form a new "receptor", and then dock your ligand to the
resulting structure.

More ambitiously, you might repeat the process with cofactor binding
modes number 2, 3, ...

Oleg

On Sat, Apr 12, 2014 at 11:25 AM, AVanheule <[hidden email]> wrote:

> Hi everyone,
>
> I have a P450 monooxygenase that I would like to use in docking. The
> structure that I have does not include the heme group. I have carried out
> two seperate dockings: I docked my heme group to my receptor, and I docked
> my ligand to my receptor. Unfortunately, when I combine those results they
> don't really make a lot of sense. They are perfectly in the same active site
> cavity, but there are minor overlaps. I figure that I should find a way to
> include the ideal docked state of my heme group (reassuringly, the
> differences between the different heme conformations are minimal, and
> literature suggests that this docking is correct) in my receptor structure,
> THEN use that new structure to dock my ligand.
>
> I have been able to combine my receptor structure and my best heme docking
> in one pdb file without problems, but the trouble starts when I read that
> pdb file in AutodockTools to create my new .pdbqt file for the second round
> of docking (with the ligand). Is this not the correct approach? How should I
> go about this?
>
> Thank you for any help,
> Kind regards
> Adriaan
>
>
>
> --
> View this message in context: http://autodock.1369657.n2.nabble.com/Dock-heme-to-P450-then-re-use-best-structure-to-dock-ligand-tp7578518.html
> Sent from the AutoDock mailing list archive at Nabble.com.
> ________________________________________________
> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---



--
Oleg Trott, Ph.D. (Columbia University)

Staff Scientist in the Olson Lab
The Scripps Research Institute

http://olegtrott.com
________________________________________________
--- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
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Re: ADL: Dock heme to P450, then re-use best structure to dock ligand

Oleg Trott
Sorry, it looks like I misread your original post.

I hope Ruth will comment on how to combine the receptor and the ligand
in ADT. In the worst case, one can do it by hand (by editing the
files).

Oleg

On Sat, Apr 12, 2014 at 11:58 AM, Oleg Trott <[hidden email]> wrote:

> Hi
>
> You probably want to dock the cofactor first, merge it with the
> receptor to form a new "receptor", and then dock your ligand to the
> resulting structure.
>
> More ambitiously, you might repeat the process with cofactor binding
> modes number 2, 3, ...
>
> Oleg
>
> On Sat, Apr 12, 2014 at 11:25 AM, AVanheule <[hidden email]> wrote:
>> Hi everyone,
>>
>> I have a P450 monooxygenase that I would like to use in docking. The
>> structure that I have does not include the heme group. I have carried out
>> two seperate dockings: I docked my heme group to my receptor, and I docked
>> my ligand to my receptor. Unfortunately, when I combine those results they
>> don't really make a lot of sense. They are perfectly in the same active site
>> cavity, but there are minor overlaps. I figure that I should find a way to
>> include the ideal docked state of my heme group (reassuringly, the
>> differences between the different heme conformations are minimal, and
>> literature suggests that this docking is correct) in my receptor structure,
>> THEN use that new structure to dock my ligand.
>>
>> I have been able to combine my receptor structure and my best heme docking
>> in one pdb file without problems, but the trouble starts when I read that
>> pdb file in AutodockTools to create my new .pdbqt file for the second round
>> of docking (with the ligand). Is this not the correct approach? How should I
>> go about this?
>>
>> Thank you for any help,
>> Kind regards
>> Adriaan
>>
>>
>>
>> --
>> View this message in context: http://autodock.1369657.n2.nabble.com/Dock-heme-to-P450-then-re-use-best-structure-to-dock-ligand-tp7578518.html
>> Sent from the AutoDock mailing list archive at Nabble.com.
>> ________________________________________________
>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>
>
>
> --
> Oleg Trott, Ph.D. (Columbia University)
>
> Staff Scientist in the Olson Lab
> The Scripps Research Institute
>
> http://olegtrott.com



--
Oleg Trott, Ph.D. (Columbia University)

Staff Scientist in the Olson Lab
The Scripps Research Institute

http://olegtrott.com
________________________________________________
--- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
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Re: ADL: Dock heme to P450, then re-use best structure to dock ligand

Ruth Huey
Hi,
________________________________________
From: [hidden email] [[hidden email]] On Behalf Of Oleg Trott [[hidden email]]
Sent: Saturday, April 12, 2014 7:21 PM
To: [hidden email]
Subject: Re: Dock heme to P450, then re-use best structure to dock ligand

Sorry, it looks like I misread your original post.

I hope Ruth will comment on how to combine the receptor and the ligand
in ADT. In the worst case, one can do it by hand (by editing the
files).

Oleg

On Sat, Apr 12, 2014 at 11:58 AM, Oleg Trott <[hidden email]> wrote:
> Hi
>
> You probably want to dock the cofactor first, merge it with the
> receptor to form a new "receptor", and then dock your ligand to the
> resulting structure.
>
Don't use ADT for this.
Instead, use a text editor to add just the ATOM/HETATM records from the docked cofactor pdbqt file to the receptor pdbqt file.
Then use the augmented pdbqt file as the receptor for your docking (without any further processing in ADT).

 -Ruth  

> More ambitiously, you might repeat the process with cofactor binding
> modes number 2, 3, ...
also possible!

> Oleg
>
> On Sat, Apr 12, 2014 at 11:25 AM, AVanheule <[hidden email]> wrote:
>> Hi everyone,
>>
>> I have a P450 monooxygenase that I would like to use in docking. The
>> structure that I have does not include the heme group. I have carried out
>> two seperate dockings: I docked my heme group to my receptor, and I docked
>> my ligand to my receptor. Unfortunately, when I combine those results they
>> don't really make a lot of sense. They are perfectly in the same active site
>> cavity, but there are minor overlaps. I figure that I should find a way to
>> include the ideal docked state of my heme group (reassuringly, the
>> differences between the different heme conformations are minimal, and
>> literature suggests that this docking is correct) in my receptor structure,
>> THEN use that new structure to dock my ligand.
>>
>> I have been able to combine my receptor structure and my best heme docking
>> in one pdb file without problems, but the trouble starts when I read that
>> pdb file in AutodockTools to create my new .pdbqt file for the second round
>> of docking (with the ligand). Is this not the correct approach? How should I
>> go about this?
>>
>> Thank you for any help,
>> Kind regards
>> Adriaan
>>
>>
>>
>> --
>> View this message in context: http://autodock.1369657.n2.nabble.com/Dock-heme-to-P450-then-re-use-best-structure-to-dock-ligand-tp7578518.html
>> Sent from the AutoDock mailing list archive at Nabble.com.
>> ________________________________________________
>> --- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
>
>
>
> --
> Oleg Trott, Ph.D. (Columbia University)
>
> Staff Scientist in the Olson Lab
> The Scripps Research Institute
>
> http://olegtrott.com



--
Oleg Trott, Ph.D. (Columbia University)

Staff Scientist in the Olson Lab
The Scripps Research Institute

http://olegtrott.com
________________________________________________
--- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---

________________________________________________
--- ADL: AutoDock List  --- http://autodock.scripps.edu/mailing_list ---
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Re: ADL: Dock heme to P450, then re-use best structure to dock ligand

AVanheule
Works like a charm. Thank you dr. Trott and dr. Huey!