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]
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>
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?
>>>
>>> _______________________________________________
>>> AMBER mailing list
>>> AMBER.ambermd.org
>>> http://lists.ambermd.org/mailman/listinfo/amber
>>
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Received on Wed Nov 25 2015 - 05:30:03 PST
