[Dock-fans] Distorted bond Angles

Trent E. Balius tbalius at aol.com
Fri Jun 17 08:04:34 PDT 2011


Hi Marco,

I did some small tests and the following two definitions seemed to work for two benzine rings attached to one another via a single bond (Biphenyl).

---------------------------------
name           aromatic-aromatic
driver_id      122
minimize       1

definition     C.ar ( C.ar ) ( C.ar )
definition     C.ar ( C.ar ) ( C.ar )
---------------------------------

or

---------------------------------
name           aromatic-aromatic
driver_id      122
minimize       1
    
definition     C.ar ( 3 C.ar ) 
definition     C.ar ( 3 C.ar ) 
---------------------------------
    
I think that I prefer the first definition. Both result in the sampling of the torsion:

Output excerpt using standard flex.defn file
-----------------------------------
VERBOSE GROWTH STATS : ANCHOR #1

31/500 anchor orients retained (max 1000) t=1.86s

No more anchor fragments to be docked.

-----------------------------------
Molecule: NONAME

 Elapsed time for docking:      5 seconds

 Anchors:               1
 Orientations:          500
 Conformations:         31

    Grid Score:          -27.257816
      Grid_vdw:          -27.257816
       Grid_es:            0.000000
    Int_energy:            0.000000

This tortion is not sampled.

Using the modified definition file:

VERBOSE GROWTH STATS : ANCHOR #1

25/500 anchor orients retained (max 1000) t=1.55s
Lyr 1-1 Segs|
Lyr:1 Seg:0 Bond:3 : Sampling 6 dihedrals C(C.ar)  C(C.ar)  C(C.ar)  C(C.ar)
Lyr:1 Seg:0 101/150 retained, Pruning: 22-score 27-clustered  t=2.66s
No more anchor fragments to be docked.

-----------------------------------
Molecule: NONAME

 Elapsed time for docking:      6 seconds

 Anchors:               1
 Orientations:          500
 Conformations:         101

    Grid Score:          -27.779678
      Grid_vdw:          -27.779678
       Grid_es:            0.000000
    Int_energy:            0.787666


The torsion was sampled.

I used the driver_id of 122 which samples 6 dihideral but the best bet would proboble be driver_id of 4:

drive_id        4
positions       4
torsions        -90 0 90 180

I think that I was mistaken about a few things in the earlier e-mails.  Sorry for the confusion and good luck.

I hope this helps,

Trent


-----Original Message-----
From: Marco <marco at chimfarm.unipg.it>
To: tbalius at aol.com
Sent: Fri, Jun 17, 2011 9:38 am
Subject: Re: [Dock-fans] Distorted bond Angles


Hi Trent,
Thank you for your kind answers, but I can't solve my problem in an "elegant
manner".

Here
http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#AtomDefinitionRules

I found the following definition:
- [Specifies atoms that must NOT be bonded to parent atom]
- (Specifies atoms that must be bonded to parent atom)

...so I edited my flex.defn file adding the following lines:

---------------------------------
name           aromatic-aromatic
driver_id      32
minimize       1

definition     C.ar ( 2 C.ar )  
definition     C.ar ( 2 C.ar )
---------------------------------

...but from the output I noted that dock can't understand what I'd like to
do.

If you remember I'm trying to sample the dihedral bond between two phenyl
rings, and to achieve a more accurate depiction of the two C.ar forming the
bond, I've also used the following lines in the flex.defn


----------------------------------
name           aromatic-aromatic
driver_id      32
minimize       1
definition     C.ar [ C.ar ] [ H ]
definition     C.ar [ C.ar ] [ H ]
-----------------------------------

....also in this case, I can't sample my bond.

On the other side, surprising, using the following lines I can sample the
bond...

 ----------------------------------
name           aromatic-aromatic
driver_id      32
minimize       1
definition     C.ar [ 2 C.ar ] 
definition     C.ar [ 2 C.ar ] 
-----------------------------------

...but due to the huge number of dihedrals I have a segmentation fault on my
machine. :(

Finally I resolved my problem with "a not too elegant" trick... changing the
mol2 atom type of my ligand input file. In particular I changed the one of
the C.ar at the end of the bond, switching it in C.2.
Obviously this trick is not feasible for a database of molecules, and the
only rational solution I found is to perform rigid dock of pre-generated
conformers.

Thank you again for your patience, 
Have a nice day!

Marco.


----
Marco Cellanetti, 
PhD Student.
Bachelor Degree in Medicinal Chemistry and Technology of Drugs

University of Perugia
Department of Medicinal Chemistry and Drug's Technology
Via del Liceo, 1 - 06123 Perugia (Italy)
Tel ++39 075 585 5169/5114



--------- Messaggio Originale --------
Da: Trent E. Balius <tbalius at aol.com>
Per: marco at chimfarm.unipg.it
<marco at chimfarm.unipg.it>,dock-fans at mailman.docking.org
<dock-fans at mailman.docking.org>
Oggetto: Re: [Dock-fans] Distorted bond Angles
Data: 16/06/11 16:35

> 
> 
>  Hi Marco,
> 
> 
> One way to check that dock is interpreting the torsion definition
correctly is to turn on the verbose flag:  You will see data about this
torsion in the verbose statistics.  See the following section from the
manual.
> 
> 
> 
> 
>
http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#GrowthTreeAndStatistics
> 
> 
> 
> Example output:
> 
> 
> 
> Lyr:2 Seg:0 Bond:5 : Sampling 3 dihedrals C4(C.ar) C3(C.3) C1(C.3) N1(N.3)
> 
> Lyr:2 Seg:0 57/63 retained, Pruning: 1-score 5-clustered (119 in growth
tree) t=22.36s
> 
> 
> 
> As you can see the first line reports information about the torsion being
sampled.
> 
> I am not sure but try modifying the definitions:
> 
> 
> 
>   name          
aromatic-aromatic
> 
>   driver_id      122
> 
>   minimize       1
> 
>   
> 
>   definition     C.ar  [ 2 C.ar ]
> 
>   definition     C.ar  [ 2 C.ar ]
> 
> 
> 
> 
> I would turn on the ability to minimize this torsion
> 
> 
> The first atom type in definition is connected to the other definition via
the torsion bond. 
> 
> I believe that the entries in brackets refers to the atoms connected to
the first atom.
> 
> 
> 
> In other words, definition C.ar [2 C.ar] means that atom C.ar has two
atoms connected to it of type C.ar as well as being connected to the other
definition entry (I think). 
> 
> 
> I hope this helps,  
> 
> 
> 
> 
> 
> 
> Trent 
> 
> 
> 
> 
> 
>  
> 
> 
> 
> 
> 
>  
> 
> 
> 
> 
> 
> -----Original Message-----
> 
> From: Marco <marco at chimfarm.unipg.it>
> 
> To: dock-fans at mailman.docking.org
> 
> Sent: Thu, Jun 16, 2011 9:08 am
> 
> Subject: Re: [Dock-fans] Distorted bond Angles
> 
> 
> 
> 
> 
> 
> 
> 
> 
> 
> 
> 
> 
> Hi all, and hi Trent!
> 
> Thank you for your previous answer.
> In these day I've tried to edit the flex.defn file but I get always the
same
> results.
> 
> I'm trying to dock a derivative of 4'Phenylcinnamic acid in my target.
> If I used the rigid protocol after the predetermination of the conformers
I
> obtain a wonderful pose, near the experimental data I have.
> 
> But if I use the flex protocol (the classic flex.in changing only the
> max_orientations to 10000) I obtain very weird poses. The orientation is
> more or less good, but the two phenyl groups are planar (while I suppose
> there is a little torsion since there are substituents on the aromatic
> rings) and the oleifin moiety is completely out of the plane...
> 
> In the flex.defn I added the following lines aimed to sample the torsional
> bond between the rings, but it doesn't work. Moreover I can't understand
the
> meaning of the round or squared brackets.
> 
> name           aromatic-aromatic
> driver_id      122
> minimize       0
> 
> definition     C.ar [ 3 C.ar ]
> definition     C.ar [ 3 C.ar ]
> 
> I'm really sorry to reply my case, but I retain is a very general one, and
I
> guess it can be useful for other dock users.
> 
> Thank you!
> 
> ----
> Marco Cellanetti, 
> PhD Student.
> Bachelor Degree in Medicinal Chemistry and Technology of Drugs
> 
> University of Perugia
> Department of Medicinal Chemistry and Drug's Technology
> Via del Liceo, 1 - 06123 Perugia (Italy)
> Tel ++39 075 585 5169/5114
> 
> 
> 
> --------- Messaggio Originale --------
> Da: dock-fans at mailman.docking.org
> Per: dock-fans at mailman.docking.org <dock-fans at mailman.docking.org>
> Oggetto: Dock-fans Digest, Vol 85, Issue 3
> Data: 10/06/11 19:22
> 
> > 
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> > Today's Topics:
> > 
> >    1. Distorted bond Angles (Marco)
> >    2. Re: Distorted bond Angles (Trent E. Balius)
> > 
> > 
> >
----------------------------------------------------------------------
> > 
> > Message: 1
> > Date: Fri, 10 Jun 2011 14:43:02 +0200
> > From: Marco <marco at chimfarm.unipg.it>
> > Subject: [Dock-fans] Distorted bond Angles
> > To: dock-fans at mailman.docking.org
> > Message-ID:
> <a9234e3a249f8c48c79a6c9d2cab533a at iris.chimfarm.unipg.it>
> > Content-Type: text/plain; charset=&quot;iso-8859-1&quot;
> > 
> > Hi all!
> > I'm a new dock user. Following the tutorial I've performed docking
studies
> > on my target. I'm actually docking a small molecule with a cinnamic
acid
> > moiety in a flexible way. Unfortunately the olefine bond in the
docking
> > solution is distorted in an unnatural manner. To overcome this
problem I
> can
> > dock in the rigid way the conformers of my small molecule, but I'd
like to
> > know if there is a way to set manually as rigid bond some bonds of my
> > molecule.
> > 
> > Any advice is very appreciated. 
> > Thank you.
> > 
> > Marco 
> > 
> > 
> > ----
> > Marco Cellanetti, 
> > PhD Student.
> > Bachelor Degree in Medicinal Chemistry and Technology of Drugs
> > 
> > University of Perugia
> > Department of Medicinal Chemistry and Drug's Technology
> > Via del Liceo, 1 - 06123 Perugia (Italy)
> > Tel ++39 075 585 5169/5114
> > 
> > 
> > 
> > 
> > ________________________________________________________________
> > Message sent using Telaen Webmail 1.2.0
> > 
> > 
> > 
> > ------------------------------
> > 
> > Message: 2
> > Date: Fri, 10 Jun 2011 10:03:43 -0400
> > From: &quot;Trent E. Balius&quot; <tbalius at aol.com>
> > Subject: Re: [Dock-fans] Distorted bond Angles
> > To: marco at chimfarm.unipg.it, dock-fans at mailman.docking.org
> > Message-ID:
<8CDF58E57EE6BE1-16E0-981FA at webmail-m137.sysops.aol.com>
> > Content-Type: text/plain; charset=&quot;us-ascii&quot;
> > 
> > 
> >  Hi Marco,
> >     
> > One approach to sample this distorted torsion is to modify the
flex.defn
> and the flex_drive.tbl files.
> >     
> > See the following:
> > http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#flexdefn
> >   http://dock.compbio.ucsf.edu/DOCK_6/dock6_manual.htm#flex_drivetbl
> > In addition consult the following:
> > http://mailman.docking.org/pipermail/dock-fans/2010-May/002360.html
> > 
> > Excerpt from flex.defn:
> > name sp3-sp3 
> > drive_id 3 
> > minimize 1 
> > definition .3 [ 3 H ] [ 3 O.co2 ] 
> > definition .3 [ 3 H ] [ 3 O.co2 ] 
> >     
> > Here you can see the the flexible definition file specifies a torsion
> angle and gives the drive type (drive_id). 
> >     
> >   Excerpt from flex_drive.tbl
> > drive_id 3 
> > positions 3 
> > torsions -60 60 180 
> > 
> >  
> > Here you can see that the flexible drive table specifies the angle to
be
> sampled for the drive type.
> > 
> > You should modify the flex.defn to have an entry for the olefine bond
and
> use of create an appropriate entry in the flex_drive.tbl file.
> >   
> > You may want to also verify that your small molecule mol2 file has
the
> correct hybridization and protonation.  
> > 
> > I hope this helps,
> > 
> > 
> >  
> > 
> > Trent E. Balius
> > Graduate Student, Rizzo Group,
> > Department of Applied Mathematics and Statistics,
> > Stony Brook University.
> > Office: Math Tower 3-129, Phone: (631) 632-8519
> > URL: http://www.ams.sunysb.edu/~tbalius/
> > 
> >  
> > 
> >  
> > 
> > -----Original Message-----
> > From: Marco <marco at chimfarm.unipg.it>
> > To: dock-fans at mailman.docking.org
> > Sent: Fri, Jun 10, 2011 8:43 am
> > Subject: [Dock-fans] Distorted bond Angles
> > 
> > 
> > Hi all!
> > I'm a new dock user. Following the tutorial I've performed docking
studies
> > on my target. I'm actually docking a small molecule with a cinnamic
acid
> > moiety in a flexible way. Unfortunately the olefine bond in the
docking
> > solution is distorted in an unnatural manner. To overcome this
problem I
> can
> > dock in the rigid way the conformers of my small molecule, but I'd
like to
> > know if there is a way to set manually as rigid bond some bonds of my
> > molecule.
> > 
> > Any advice is very appreciated. 
> > Thank you.
> > 
> > Marco 
> > 
> > 
> > ----
> > Marco Cellanetti, 
> > PhD Student.
> > Bachelor Degree in Medicinal Chemistry and Technology of Drugs
> > 
> > University of Perugia
> > Department of Medicinal Chemistry and Drug's Technology
> > Via del Liceo, 1 - 06123 Perugia (Italy)
> > Tel ++39 075 585 5169/5114
> > 
> > 
> > 
> > 
> > ________________________________________________________________
> > Message sent using Telaen Webmail 1.2.0
> > 
> > _______________________________________________
> > Dock-fans mailing list
> > Dock-fans at mailman.docking.org
> > http://mailman.docking.org/mailman/listinfo/dock-fans
> > 
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