[gmx-users] Getting ligand's topology

Justin Lemkul jalemkul at vt.edu
Wed Aug 22 21:26:15 CEST 2018 


On 8/22/18 3:23 PM, Mahdi Sobati Nezhad wrote:
> can I use SWISSPARAM or MATCH servers?!

You can use whatever you like, but a good reviewer is always going to 
ask you how you validated any topology you get from such services. And 
what's more, *you* should care just as much as that skeptical reviewer. 
If any procedure gives you a topology that requires adjustment, you 
still have to do that work. If the server doesn't tell you about how 
good the topology is, you should still do the work to investigate it 
yourself.

-Justin

> On Wed, 22 Aug 2018 23:50 Justin Lemkul, <jalemkul at vt.edu> wrote:
>
>>
>> On 8/22/18 3:18 PM, Mahdi Sobati Nezhad wrote:
>>> Thanks, do acpype is for charmm?!
>>>
>> No, it is for AMBER.
>>
>> -Justin
>>
>>> On Wed, 22 Aug 2018 09:43 Bratin Kumar Das, <177cy500.bratin at nitk.edu.in
>>>
>>> wrote:
>>>
>>>> Hi
>>>>      You can use acpype for generating the ligand topology. It's simple
>> and
>>>> easy
>>>>
>>>> On Mon, Aug 20, 2018 at 5:03 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>>>>
>>>>> On 8/20/18 2:40 AM, Mahdi Sobati Nezhad wrote:
>>>>>
>>>>>> thanks for your taking time. and so on for a begginer like me there is
>>>> no
>>>>>> any way
>>>>>>
>>>>> Well, there is if you're willing to invest the time in learning some
>>>>> challenging concepts and some new software. But no one should expect
>> that
>>>>> for any given ligand, there is a perfect tool for magically giving you
>> a
>>>>> perfect topology. That's rarely the case.
>>>>>
>>>>> -Justin
>>>>>
>>>>>
>>>>> On Mon, 20 Aug 2018 00:29 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.
>>>>>>>
>>>>>>> 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
>>>>>>>>>>>>> --
>>>>>>>>>>>>> Gromacs Users mailing list
>>>>>>>>>>>>>
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>>>>>>>>>>>>> posting!
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>>>>>>>>>>>>> --
>>>>>>>>>>>> *Regards,*
>>>>>>>>>>>> *Rahul *
>>>>>>>>>>>> --
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>>>>>>>>>> --
>>>>>>>>>> *Regards,*
>>>>>>>>>> *Rahul *
>>>>>>>>>> --
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>>>>>>>>>>
>>>>>>>>> --
>>>>>>>>> Gromacs Users mailing list
>>>>>>>>>
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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
>>>>>>>
>>>>>>> ==================================================
>>>>>>>
>>>>>>> --
>>>>>>> Gromacs Users mailing list
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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
>>>>>
>>>>> ==================================================
>>>>>
>>>>> --
>>>>> Gromacs Users mailing list
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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
>>
>> ==================================================
>>
>> --
>> Gromacs Users mailing list
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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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