Thanks again,
Yes I know all this, but I didn’t know a nitrogen can have a tetrahedral symmetry without being charged…. (this molecule is zero charged correct?). I downloaded installed and are able to see the molecule with avogadro, looks great.
Could you be so kind to explain me how to add a second hydrogen to the N1 from the paper….?
It is just to reproduce the tutorial, and then I will do the calculations on my molecules.
Thanks!!
Dr. Fabian Glaser
Head of the Structural Bioinformatics section
Bioinformatics Knowledge Unit - BKU
The Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering
Technion - Israel Institute of Technology, Haifa 32000, ISRAEL
fglaser at technion dot ac dot il
Tel: +972 4 8293701
http://bku.technion.ac.il
> On 25 Nov 2015, at 3:03 PM, <hannes.loeffler.stfc.ac.uk> <hannes.loeffler.stfc.ac.uk> wrote:
>
> I don't think this is weird at all.
>
> Crystal structures will most likely not have any hydrogens resolved. What I guess is happening is that some software will add hydrogens to fill the valencies. But protonation states, and more generally tautomeric states. are a function of the environment e.g. pH or the medium the molecule is embedded in. This is just basic chemistry. I would expect that particular nitrogen to be protonated in even moderately acidic aqueous solutions. In a protein environment, when that particular group binds for instance, the situation may be different again.
>
> Interactive graphical tools like chimera or avogadro (the ones I happen to know, but I'm sure there are many others) can be used to "draw" atddtional atoms.
>
> Cheers,
> Hannes.
>
> ________________________________________
> From: Fabian gmail [fabian.glaser.gmail.com <mailto:fabian.glaser.gmail.com>]
> Sent: 25 November 2015 12:26
> To: AMBER Mailing List
> Subject: Re: [AMBER] free energy of solvation of small molecules
>
> Your are right!
>
> But the geometry of N1 is different on the drug bank….
>
> http://www.rcsb.org/pdb/ligand/ligandsummary.do?hetId=SKF&sid=1HNN <http://www.rcsb.org/pdb/ligand/ligandsummary.do?hetId=SKF&sid=1HNN><http://www.rcsb.org/pdb/ligand/ligandsummary.do?hetId=SKF&sid=1HNN <http://www.rcsb.org/pdb/ligand/ligandsummary.do?hetId=SKF&sid=1HNN>>
>
> Very weird, in any case could you please direct me how to change it?
>
> This cannot be a charged nitrogen…. the formal charge is zero.
>
> Very weird.
>
> thanks!!
>
> Fabian
>
>
>
>
> Dr. Fabian Glaser
> Head of the Structural Bioinformatics section
>
> Bioinformatics Knowledge Unit - BKU
> The Lorry I. Lokey Interdisciplinary Center for Life Sciences and Engineering
> Technion - Israel Institute of Technology, Haifa 32000, ISRAEL
>
> fglaser at technion dot ac dot il
> Tel: +972 4 8293701
> http://bku.technion.ac.il
>
>
>> On 25 Nov 2015, at 1:10 PM, Hannes Loeffler <Hannes.Loeffler.stfc.ac.uk> wrote:
>>
>> Your N1 is not protonated as it is in the paper.
>>
>> On Wed, 25 Nov 2015 12:39:59 +0200
>> Fabian gmail <fabian.glaser.gmail.com> wrote:
>>
>>> Thanks for the detailed answer
>>>
>>> Well I tried several times to run reduce and antechamber with
>>> different options (e.g. with -Xplor parameter in reduce) but the
>>> names are not identical not in the PDB, but more importantly not in
>>> the mol2 file. And the charges are very different. The authors do use
>>> GAFF but with RESP for partial charges….
>>>
>>> "Partial charges for ligands were obtained using RESP38 fi tting for
>>> the electrostatic potentials calculated using Gaussian0339 at the
>>> Hartree− Fock/6-31G* level of theory."
>>>
>>> As you can see the PDB indeed names the ligand correctly SKF, and so
>>> the sqm.pdb file, and indeed I used AM1-BCC charge method, but the
>>> charges and atoms types are indeed quite different, I paste both my
>>> results and their results for comparison…. I guess I will try anyway
>>> and see how different the results are.
>>>
>>> I guess the results will be different, but in any case I am looking
>>> for a certain degree of reproducibility before I start playing with
>>> my molecules, if the results are completely wrong well… I will
>>> rethink.
>>>
>>> THanks!!
>>>
>>> Fabian
>>>
>>>
>>> MY RESULTS
>>>
>>> .<TRIPOS>MOLECULE
>>> SKF
>>> 26 27 1 0 0
>>> SMALL
>>> bcc
>>>
>>>
>>> .<TRIPOS>ATOM
>>> 1 C4 28.3480 46.0370 16.7830 ca 3001 SKF
>>> -0.157000 2 C5 27.8990 45.5320 15.5700 ca 3001
>>> SKF -0.017000 3 C6 27.8220 44.1470 15.3850 ca
>>> 3001 SKF -0.387500 4 C7 28.1930 43.2860 16.4100
>>> ca 3001 SKF -0.010000 5 S 27.2610 43.4900
>>> 13.8470 sy 3001 SKF 1.528200 6 C8 28.6420
>>> 43.7900 17.6160 ca 3001 SKF -0.141300 7 C9
>>> 28.7200 45.1740 17.8070 ca 3001 SKF -0.008300 8
>>> O1 27.4850 44.4300 12.7700 o 3001 SKF -0.658800
>>> 9 O2 25.8660 43.1330 13.8730 o 3001 SKF
>>> -0.658800 10 N 28.1050 42.1870 13.5730 n3 3001
>>> SKF -1.026700 11 C1 28.9650 42.8430 18.7440 c3
>>> 3001 SKF 0.194100 12 C2 29.2110 44.8480 20.1940
>>> c3 3001 SKF 0.150800 13 C3 29.4880 45.7050
>>> 18.9780 c3 3001 SKF -0.087100 14 N1 29.7000
>>> 43.4830 19.8600 n3 3001 SKF -0.793200 15 HC32
>>> 30.4380 45.7060 18.7810 hc 3001 SKF 0.062700 16
>>> HC31 29.2340 46.6240 19.1540 hc 3001 SKF 0.062700
>>> 17 HC22 29.6670 45.1980 20.9750 h1 3001 SKF
>>> 0.059700 18 HC21 28.2630 44.8360 20.4000 h1 3001
>>> SKF 0.059700 19 HC12 28.1400 42.4640 19.0850 h1
>>> 3001 SKF 0.066200 20 HC11 29.4940 42.1070 18.3980
>>> h1 3001 SKF 0.066200 21 HN1 30.3490 43.1010
>>> 20.2760 hn 3001 SKF 0.353800 22 HC7 28.1370
>>> 42.3270 16.2790 ha 3001 SKF 0.153000 23 HC5
>>> 27.6400 46.1350 14.8560 ha 3001 SKF 0.152000 24
>>> HC4 28.4020 46.9960 16.9160 ha 3001 SKF 0.141000
>>> 25 H2N 27.9670 41.7280 12.8590 hn 3001 SKF
>>> 0.446800 26 H1N 28.7030 41.9350 14.1370 hn 3001
>>> SKF 0.446800 @<TRIPOS>BOND
>>>
>>>
>>> THEIR CHARGES AND ATOM TYPES
>>>
>>> Atom Name
>>> Atom Type
>>> Partial Charge
>>> O1
>>> S1
>>> O2
>>> N2
>>> H12
>>> H13
>>> C1
>>> C6
>>> H5
>>> C2
>>> H3
>>> C3
>>> H4
>>> C4
>>> C5
>>> C9
>>> H7
>>> H8
>>> N1
>>> H1
>>> H2
>>> C8
>>> H10
>>> H11
>>> C7
>>> H6
>>> H9
>>> o
>>> sy
>>> o
>>> n3
>>> hn
>>> hn
>>> ca
>>> ca
>>> ha
>>> ca
>>> ha
>>> ca
>>> ha
>>> ca
>>> ca
>>> c3
>>> hx
>>> hx
>>> n4
>>> hn
>>> hn
>>> c3
>>> hx
>>> hx
>>> c3
>>> hc
>>> hc
>>> -0.573668
>>> 1.232538
>>> -0.573668
>>> -1.037186
>>> 0.469850
>>> 0.469850
>>> -0.028732
>>> -0.216911
>>> 0.200250
>>> -0.129610
>>> 0.216974
>>> -0.225853
>>> 0.183828
>>> 0.053522
>>> 0.065648
>>> -0.178191
>>> 0.172836
>>> 0.172836
>>> -0.313324
>>> 0.348583
>>> 0.348583
>>> -0.090633
>>> 0.141132
>>> 0.141132
>>> 0.017190
>>> 0.066512
>>> 0.066512
>>>
>>>
>>>
>>> Dr. Fabian Glaser
>>> Head of the Structural Bioinformatics section
>>>
>>> Bioinformatics Knowledge Unit - BKU
>>> The Lorry I. Lokey Interdisciplinary Center for Life Sciences and
>>> Engineering Technion - Israel Institute of Technology, Haifa 32000,
>>> ISRAEL
>>>
>>> fglaser at technion dot ac dot il
>>> Tel: +972 4 8293701
>>> http://bku.technion.ac.il
>>>
>>>
>>>> On 25 Nov 2015, at 12:16 PM, Hannes Loeffler
>>>> <Hannes.Loeffler.stfc.ac.uk> wrote:
>>>>
>>>> Dear Fabian.
>>>>
>>>> if the authors have used GAFF you should be able to obtain the same
>>>> atoms types. Charges will of course vary depending on the
>>>> derivation method you use. Principally free energies are dependent
>>>> on force field parameters but I won't be able to tell you how much
>>>> that would be (there are a few papers out there which compare e.g.
>>>> GAFF to OPLS).
>>>>
>>>> A few points to check:
>>>> Reduce reads a dictionary of known PDB structures so make sure that
>>>> your PDB file does indeed name the ligand as SKF. Check reduce's
>>>> output to make sure that is true. Make sure that the hydrogens you
>>>> have obtained are the same as in the paper. If so you should get
>>>> the same atom types.
>>>>
>>>> The charge models used for the AMBER family of force fields is
>>>> basically RESP or AM1/BCC (there are some exceptions but look that
>>>> up in the manual).
>>>>
>>>> Cheers,
>>>> Hannes
>>>>
>>>>
>>>> On Wed, 25 Nov 2015 11:43:36 +0200
>>>> Fabian gmail <fabian.glaser.gmail.com> wrote:
>>>>
>>>>> Dear Hannes,
>>>>>
>>>>> I am trying to reproduce initially the results from the Kaus et al
>>>>> paper you mention for the first ligand
>>>>> ( 7-sulfamoyl-1,2,3,4-tetrahydroisoquinolinium), now if I am
>>>>> understand correctly first I need to obtain the mol2 file using
>>>>> antechamber with gaff model, starting from the PDB structure of
>>>>> this ligand this is what I tried to do using this commands:
>>>>>
>>>>> reduce SKF_A.pdb > SKF_hyd.pdb
>>>>> antechamber -i SKF_hyd.pdb -fi pdb -o SKF.mol2 -fo mol2 -c bcc -s 2
>>>>>
>>>>> This yields completely different atom types and charges as compared
>>>>> to the paper of Kaus, as expected since they used RESP model and I
>>>>> used AMB1-BCC, but I don’t have gaussian….
>>>>>
>>>>> Do you think the final DG value will be highly different using the
>>>>> bcc model or could you recommend to use a different model of those
>>>>> included in amber that I could use, which will provide more similar
>>>>> charges to the ones on the paper?
>>>>>
>>>>> Will those values highly impact the final results?
>>>>
>>>> _______________________________________________
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>>>
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>>
>>
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Received on Wed Nov 25 2015 - 07:30:05 PST
