[gmx-users] Getting ligand's topology

Mon Aug 20 06:50:29 CEST 2018

On Mon, Aug 20, 2018 at 1:29 AM Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 8/19/18 10:20 AM, RAHUL SURESH wrote:
> > Hi.
> >
> > First, I feel grimaces users may not entertain other discussions in
> grimace
> > forum. You can directly mail me if it’s something apart from gromacs.
> >
> > Then, I am not sure about other servers.
> >
> > Looking at your str file, I would say that it definitely need some work
> on
> > our molecule. As I said before try zinc database.
>
> I don't see how the ZINC database is relevant. Either the .mol2
> submitted to the CGenFF server is valid or it is not.
>

Dear Dr. Justin

I have noticed few too many times that .mol2 file from Zinc database got
less penalties compared to the strcuture from other databases in case of
CgenFF.

>
> CGenFF is nice in that it tells you the potential problems with the
> ligand topology. AFAIK, no other servers do. You get a "black box"
> output that you're supposed to trust. The areas pinpointed by CGenFF
> should be examined carefully. The parameters may actually be fine, but
> the penalties are there to tell the user when there is a functional
> group that is not well described by existing molecules in the CGenFF
> database, from which the analogies are made.
>
> There is a CGenFF tutorial available online that walks a user through
> the whole process. It requires subdividing a molecule into units that
> can be parametrized easily; large molecules should always be broken down
> into manageable pieces that have all the necessary degrees of freedom.
>
> The tutorial materials can be accessed here:
> http://mackerell.umaryland.edu/~kenno/cgenff/download.php
>
> CHARMM/CGenFF parametrization assumes some familiarity with QM
> calculations (geometry optimizations, potential energy scans,
> interaction energies) but the methodology is published in great detail,
> and the CGenFF paper itself is a worked example of how to parametrize a
> molecule. While the developers have made every effort to make the
> methodology publicly available, ligand parametrization and refinement is
> still an advanced concept that is best suited for experienced users, as
> knowledge of fundamental principles of MD, QM, and empirical energy
> functions is required.
>
> -Justin
>
> > Thank you
> >
> >
> > On Sun, 19 Aug 2018 at 1:37 PM, Mahdi Sobati Nezhad <
> > mahdisobatinezhad at gmail.com> wrote:
> >
> >> thanks.
> >> if I use MATCH server or swissparam, I can trust to their results?!
> >>
> >> And this is my error when I use CGenFF:
> >> "readmol2 warning: non-unique atoms were renamed. Now processing
> molecule
> >> mae ..."
> >>
> >> And this is my output of penalty:
> >>
> >> * Toppar stream file generated by * CHARMM General Force Field (CGenFF)
> >> program version 2.2.0 * For use with CGenFF version 4.0 * read rtf card
> >> append * Topologies generated by * CHARMM General Force Field (CGenFF)
> >> program version 2.2.0 * 36 1 ! "penalty" is the highest penalty score of
> >> the associated parameters. ! Penalties lower than 10 indicate the
> analogy
> >> is fair; penalties between 10 ! and 50 mean some basic validation is
> >> recommended; penalties higher than ! 50 indicate poor analogy and
> mandate
> >> extensive validation/optimization. RESI mae 0.000 ! param penalty=
> 198.400
> >> ; charge penalty= 142.287 GROUP ! CHARGE CH_PENALTY ATOM C1 CG2R61
> 0.227 !
> >> 0.000 ATOM C2 CG2R61 -0.117 ! 2.688 ATOM C3 CG2R61 -0.003 ! 5.191 ATOM
> C4
> >> CG2R61 -0.117 ! 2.688 ATOM C5 CG2R61 0.227 ! 0.000 ATOM C6 CG2R61 0.217
> !
> >> 0.000 ATOM H1 HGR61 0.115 ! 0.000 ATOM H2 HGR61 0.115 ! 0.000 ATOM O1
> OG301
> >> -0.391 ! 0.000 ATOM O2 OG301 -0.391 ! 0.000 ATOM O3 OG301 -0.391 ! 0.000
> >> ATOM C7 CG331 -0.100 ! 0.000 ATOM H3 HGA3 0.090 ! 0.000 ATOM H4 HGA3
> 0.090
> >> ! 0.000 ATOM H5 HGA3 0.090 ! 0.000 ATOM C8 CG331 -0.100 ! 0.000 ATOM H6
> >> HGA3 0.090 ! 0.000 ATOM H7 HGA3 0.090 ! 0.000 ATOM H8 HGA3 0.090 ! 0.000
> >> ATOM C9 CG331 -0.100 ! 0.000 ATOM H9 HGA3 0.090 ! 0.000 ATOM H10 HGA3
> 0.090
> >> ! 0.000 ATOM H11 HGA3 0.090 ! 0.000 ATOM C10 CG3C51 0.317 ! 142.287
> ATOM N1
> >> NG3C51 -0.343 ! 101.066 ATOM C11 CG321 -0.072 ! 70.919 ATOM H12 HGA2
> 0.090
> >> ! 2.500 ATOM H13 HGA2 0.090 ! 2.500 ATOM C12 CG2R53 0.464 ! 90.248 ATOM
> N2
> >> NG2R50 -0.515 ! 21.469 ATOM N3 NG3C51 -0.417 ! 87.522 ATOM H14 HGP1
> 0.341 !
> >> 3.424 ATOM C13 CG321 0.028 ! 26.713 ATOM H15 HGA2 0.090 ! 2.659 ATOM N4
> >> NG3N1 -0.689 ! 58.305 ATOM C14 CG2R61 0.140 ! 19.097 ATOM C15 CG2R61
> -0.110
> >> ! 13.488 ATOM C16 CG2R61 0.036 ! 13.718 ATOM C17 CG2R61 -0.112 ! 0.000
> ATOM
> >> H16 HGR61 0.115 ! 0.000 ATOM C18 CG2R61 0.071 ! 0.000 ATOM C19 CG2R61
> >> -0.089 ! 0.000 ATOM H17 HGR61 0.115 ! 0.000 ATOM S SG311 -0.210 !
> 105.411
> >> ATOM H18 HGP3 0.160 ! 4.359 ATOM H19 HGR62 0.144 ! 0.000 ATOM Cl1 CLGR1
> >> -0.152 ! 2.500 ATOM Cl2 CLGR1 -0.167 ! 0.000 ATOM HXT1 HGA1 0.090 !
> 5.954
> >> ATOM HXT2 HGA2 0.090 ! 2.659 ATOM HN HGP1 0.394 ! 9.368 ATOM LP1 LPH
> 0.050
> >> ! on Cl1 ATOM LP2 LPH 0.050 ! on Cl2
> >>
> >>
> >> Thanks for your taking time
> >>
> >>
> >> On Sat, 18 Aug 2018 22:31 RAHUL SURESH, <drrahulsuresh at gmail.com>
> wrote:
> >>
> >>> I cannot assist you much with the description of your ligand. But what
> I
> >>> have seen is, ring with N shows maximum penalities in most cases.
> >>>
> >>> When you optimise with mp2, the structure shows no much changes.
> >>> So penalty is same most time.
> >>>
> >>> Try to download file from Zinc15 database which is most preferred file
> >>>   cgenff. Still the penalty may exist in cse of N in ring. It could be
> >>> optimised using ffTK. Again I find your structure is pretty big which
> >> will
> >>> be time consuming. Or you have to adapt divide and conquer method,
> which
> >> is
> >>> going to be complicated. So it’s your wise choice always. Maybe others,
> >>> especially Dr. Justin or Dr. Mark could give you a better soln.
> >>>
> >>> Thank you
> >>>
> >>> On Sat, 18 Aug 2018 at 10:17 PM, Mahdi Sobati Nezhad <
> >>> mahdisobatinezhad at gmail.com> wrote:
> >>>
> >>>> Thanks for your help.
> >>>> my ligand is three rings that connects with a carbon and this rings
> >> have
> >>>> Nitrogen, oxygen, sulfur, carbon and Chlor...
> >>>> And high penaltys are just for that ring that contains Nitrogen,
> carbon
> >>> and
> >>>> sulfur
> >>>> And so on my choice is just using ffTK?!
> >>>>
> >>>>
> >>>> On Sat, 18 Aug 2018 21:05 RAHUL SURESH, <drrahulsuresh at gmail.com>
> >> wrote:
> >>>>> Hi.
> >>>>>
> >>>>> To resolve the penalties are bit complicated. Tools like ffTK can
> >> help
> >>>> you
> >>>>> do it. But output from ffTK is as in charmm and henceforth it take
> >>>>> additional work ( was difficult for me ) to modify it to Gromacs
> >>>> acceptable
> >>>>> format.
> >>>>>
> >>>>> I personally don’t appreciate this method as it is very time
> >> consuming
> >>> if
> >>>>> your structure is big and having penalties in dihedrals which again
> >>> make
> >>>> it
> >>>>> complicated.
> >>>>> Thank you
> >>>>>
> >>>>> On Sat, 18 Aug 2018 at 7:02 PM, Mahdi Sobati Nezhad <
> >>>>> mahdisobatinezhad at gmail.com> wrote:
> >>>>>
> >>>>>> Hi
> >>>>>> I'm a begginer in taking ligand's topology from CGENFF and my
> >> '.str'
> >>>> file
> >>>>>> have some high penalty numbers. What I can do?!
> >>>>>> And how I can do validation and optimization?!
> >>>>>> I read the FAQ in its server but I don't understand!!!
> >>>>>> Thanks
> >>>>>> --
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> >>>>> --
> >>>>> *Regards,*
> >>>>> *Rahul *
> >>>>> --
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> >>> *Regards,*
> >>> *Rahul *
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> --
> ==================================================
>
> Justin A. Lemkul, Ph.D.
> Assistant Professor
> Virginia Tech Department of Biochemistry
>
> 303 Engel Hall
> 340 West Campus Dr.
> Blacksburg, VA 24061
>
> jalemkul at vt.edu | (540) 231-3129
> http://www.thelemkullab.com
>
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-- 
*Regards,*
*Rahul *