The structure in the paper is protonated at the nitrogen which means
that the total charge is +1.
In Avogadro you should have a pencil icon in one of the top toolbars,
otherwise Settings->Toolbars->Tools. When you click on it you should
see a selection of elements in the left. Choose hyrogen, click your N
while dragging away the new hydrogen. Extensions->Optimise Geometry if
you wish.
Cheers,
Hannes.
On Wed, 25 Nov 2015 17:15:06 +0200
Fabian gmail <fabian.glaser.gmail.com> wrote:
> 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?
> >>>>
> >>>> _______________________________________________
> >>>> AMBER mailing list
> >>>> AMBER.ambermd.org
> >>>> http://lists.ambermd.org/mailman/listinfo/amber
> >>>
> >>> _______________________________________________
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> >>
> >>
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Received on Wed Nov 25 2015 - 08:00:03 PST
