[gmx-users] Query- Ligand parametrization

Justin Lemkul jalemkul at vt.edu
Sun Mar 29 05:21:03 CEST 2015



On 3/28/15 8:36 AM, Priya Das wrote:
> This is the Paramchem generated file.
>
> * Toppar stream file generated by
> * CHARMM General Force Field (CGenFF) program version 0.9.7.1 beta
> * For use with CGenFF version 2b8
> *
>
> read rtf card append
> * Topologies generated by
> * CHARMM General Force Field (CGenFF) program version 0.9.7.1 beta
> * using valence-based bond orders
> *
> 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 Pose         0.000 ! param penalty= 117.000 ; charge penalty=  37.947
> GROUP            ! CHARGE   CH_PENALTY
> ATOM N      NG311  -0.299 !   37.947

Check interactions with water here; the penalty is not that bad but you'll want 
to check.

> ATOM C1     CG311  -0.102 !    9.362
> ATOM C2     CG311  -0.102 !   24.826
> ATOM C3     CG311  -0.092 !   12.017
> ATOM C4     CG321  -0.181 !   19.898
> ATOM C5     CG321  -0.167 !   18.342
> ATOM C6     CG321  -0.165 !    0.000
> ATOM C7     CG311  -0.094 !   17.735
> ATOM C8     CG321  -0.183 !   18.342
> ATOM C9     CG321  -0.217 !   15.714
> ATOM H      HGPAM1  0.345 !    7.962
> ATOM C10    CG321  -0.184 !   18.342
> ATOM C11    CG321  -0.181 !   15.714
> ATOM C12    CG331  -0.271 !    0.030
> ATOM C13    CG321  -0.180 !    0.030
> ATOM C14    CG321  -0.176 !    0.030
> ATOM C15    CG331  -0.271 !    0.030
> ATOM H2     HGA1    0.090 !    1.100
> ATOM H3     HGA1    0.090 !    2.536
> ATOM H4     HGA1    0.090 !    0.000
> ATOM H5     HGA2    0.090 !    0.000
> ATOM H6     HGA2    0.090 !    0.000
> ATOM H7     HGA2    0.090 !    0.750
> ATOM H8     HGA2    0.090 !    0.750
> ATOM H9     HGA2    0.090 !    0.000
> ATOM H10    HGA2    0.090 !    0.000
> ATOM H11    HGA1    0.090 !    2.536
> ATOM H12    HGA2    0.090 !    0.750
> ATOM H13    HGA2    0.090 !    0.750
> ATOM H14    HGA2    0.090 !    0.000
> ATOM H15    HGA2    0.090 !    0.000
> ATOM H16    HGA2    0.090 !    0.750
> ATOM H17    HGA2    0.090 !    0.750
> ATOM H18    HGA2    0.090 !    0.000
> ATOM H19    HGA2    0.090 !    0.000
> ATOM H20    HGA3    0.090 !    0.000
> ATOM H21    HGA3    0.090 !    0.000
> ATOM H22    HGA3    0.090 !    0.000
> ATOM H23    HGA2    0.090 !    0.000
> ATOM H24    HGA2    0.090 !    0.000
> ATOM H25    HGA2    0.090 !    0.000
> ATOM H26    HGA2    0.090 !    0.000
> ATOM H27    HGA3    0.090 !    0.000
> ATOM H28    HGA3    0.090 !    0.000
> ATOM H29    HGA3    0.090 !    0.000
>                 ! Bond order
> BOND N    H    ! 1
> BOND N    C2   ! 1
> BOND N    C7   ! 1
> BOND C1   C4   ! 1
> BOND C1   C3   ! 1
> BOND C1   C2   ! 1
> BOND C2   C5   ! 1
> BOND C3   C13  ! 1
> BOND C3   C6   ! 1
> BOND C4   C8   ! 1
> BOND C5   C9   ! 1
> BOND C6   C9   ! 1
> BOND C7   C8   ! 1
> BOND C7   C10  ! 1
> BOND C10  C11  ! 1
> BOND C11  C12  ! 1
> BOND C13  C14  ! 1
> BOND C14  C15  ! 1
> BOND C1   H2   ! 1
> BOND C2   H3   ! 1
> BOND C3   H4   ! 1
> BOND C4   H5   ! 1
> BOND C4   H6   ! 1
> BOND C5   H7   ! 1
> BOND C5   H8   ! 1
> BOND C6   H9   ! 1
> BOND C6   H10  ! 1
> BOND C7   H11  ! 1
> BOND C8   H12  ! 1
> BOND C8   H13  ! 1
> BOND C9   H14  ! 1
> BOND C9   H15  ! 1
> BOND C10  H16  ! 1
> BOND C10  H17  ! 1
> BOND C11  H18  ! 1
> BOND C11  H19  ! 1
> BOND C12  H20  ! 1
> BOND C12  H21  ! 1
> BOND C12  H22  ! 1
> BOND C13  H23  ! 1
> BOND C13  H24  ! 1
> BOND C14  H25  ! 1
> BOND C14  H26  ! 1
> BOND C15  H27  ! 1
> BOND C15  H28  ! 1
> BOND C15  H29  ! 1
>
> END
>
> read param card flex append
> * Parameters generated by analogy by
> * CHARMM General Force Field (CGenFF) program version 0.9.7.1 beta
> *
>
> ! 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.
>
> BONDS
> CG311  CG311   222.50     1.5000 ! PROT alkane update, adm jr., 3/2/92
> CG311  CG321   222.50     1.5380 ! PROT alkane update, adm jr., 3/2/92
> CG311  NG311   263.00     1.4740 ! Pose , from CG321 NG311, PENALTY= 4
> CG311  HGA1    309.00     1.1110 ! PROT alkane update, adm jr., 3/2/92
> CG321  CG321   222.50     1.5300 ! PROT alkane update, adm jr., 3/2/92
> CG321  CG331   222.50     1.5280 ! PROT alkane update, adm jr., 3/2/92
> CG321  HGA2    309.00     1.1110 ! PROT alkane update, adm jr., 3/2/92
> CG331  HGA3    322.00     1.1110 ! PROT alkane update, adm jr., 3/2/92
> NG311  HGPAM1  447.80     1.0190 ! AMINE aliphatic amines
>

Bonds are OK.

> ANGLES
> CG311  CG311  CG311    53.35    111.00    8.00   2.56100 ! PROT alkane
> update, adm jr., 3/2/92
> CG311  CG311  CG321    53.35    111.00    8.00   2.56100 ! PROT alkane
> update, adm jr., 3/2/92
> CG311  CG311  NG311    43.70    112.20 ! Pose , from CG331 CG321
> NG311, PENALTY= 5.5
> CG311  CG311  HGA1     34.50    110.10   22.53   2.17900 ! PROT alkane
> update, adm jr., 3/2/92
> CG321  CG311  CG321    58.35    113.50   11.16   2.56100 ! LIPID glycerol
> CG321  CG311  NG311    43.70    112.20 ! Pose , from CG331 CG321
> NG311, PENALTY= 4.9
> CG321  CG311  HGA1     34.50    110.10   22.53   2.17900 ! PROT alkane
> update, adm jr., 3/2/92
> NG311  CG311  HGA1     32.40    109.50   50.00   2.13000 ! Pose , from
> NG311 CG321 HGA2, PENALTY= 4
> CG311  CG321  CG321    58.35    113.50   11.16   2.56100 ! PROT alkanes
> CG311  CG321  HGA2     33.43    110.10   22.53   2.17900 ! PROT alkanes
> CG321  CG321  CG321    58.35    113.60   11.16   2.56100 ! PROT alkane
> update, adm jr., 3/2/92
> CG321  CG321  CG331    58.00    115.00    8.00   2.56100 ! PROT alkane
> update, adm jr., 3/2/92
> CG321  CG321  HGA2     26.50    110.10   22.53   2.17900 ! PROT alkane
> update, adm jr., 3/2/92
> CG331  CG321  HGA2     34.60    110.10   22.53   2.17900 ! PROT alkane
> update, adm jr., 3/2/92
> HGA2   CG321  HGA2     35.50    109.00    5.40   1.80200 ! PROT alkane
> update, adm jr., 3/2/92
> CG321  CG331  HGA3     34.60    110.10   22.53   2.17900 ! PROT alkane
> update, adm jr., 3/2/92
> HGA3   CG331  HGA3     35.50    108.40    5.40   1.80200 ! PROT alkane
> update, adm jr., 3/2/92
> CG311  NG311  CG311    40.50    112.20    5.00   2.42170 ! Pose , from
> CG3AM1 NG311 CG3AM1, PENALTY= 35

This is the only really concerning entry among the angles.  Verify with a 
3-point scan.

> CG311  NG311  HGPAM1   35.00    111.00 ! Pose , from CG321 NG311
> HGPAM1, PENALTY= 0.6
>
> DIHEDRALS
> CG311  CG311  CG311  CG321      0.5000  4   180.00 ! NA bkb
> CG311  CG311  CG311  NG311      0.1400  3     0.00 ! Pose , from CG311
> CG311 CG311 OG311, PENALTY= 38
> CG311  CG311  CG311  HGA1       0.1950  3     0.00 ! NA, sugar
> CG321  CG311  CG311  CG321      0.5000  4   180.00 ! NA, sugar
> CG321  CG311  CG311  NG311      0.2000  3   180.00 ! Pose , from CG321
> CG311 CG321 OG302, PENALTY= 37.5
> CG321  CG311  CG311  HGA1       0.1950  3     0.00 ! NA, sugar
> NG311  CG311  CG311  HGA1       0.1600  3     0.00 ! Pose , from NG311
> CG321 CG331 HGA3, PENALTY= 15
> HGA1   CG311  CG311  HGA1       0.1950  3     0.00 ! NA, sugar
> CG311  CG311  CG321  CG321      0.2000  3     0.00 ! CHL1, Cholesterol
> reset to default by kevo
> CG311  CG311  CG321  HGA2       0.1950  3     0.00 ! NA, sugar
> CG321  CG311  CG321  CG321      0.2000  3     0.00 ! PROT alkane
> update, adm jr., 3/2/92
> CG321  CG311  CG321  HGA2       0.1950  1     0.00 ! NA, sugar
> NG311  CG311  CG321  CG321      0.1950  3     0.00 ! Pose , from NG3P2
> CG314 CG321 CG321, PENALTY= 37
> NG311  CG311  CG321  HGA2       0.1600  3     0.00 ! Pose , from NG311
> CG321 CG331 HGA3, PENALTY= 10
> HGA1   CG311  CG321  CG321      0.1950  3     0.00 ! NA abasic nucleoside
> HGA1   CG311  CG321  HGA2       0.1950  3     0.00 ! NA, sugar
> CG311  CG311  NG311  CG311      2.5000  1   180.00 ! Pose , from NG311
> CG321 NG311 CG2R61, PENALTY= 117
> CG311  CG311  NG311  CG311      1.5000  2     0.00 ! Pose , from NG311
> CG321 NG311 CG2R61, PENALTY= 117
> CG311  CG311  NG311  CG311      0.5000  3     0.00 ! Pose , from NG311
> CG321 NG311 CG2R61, PENALTY= 117
> CG311  CG311  NG311  HGPAM1     0.1000  3     0.00 ! Pose , from CG331
> CG321 NG311 HGP1, PENALTY= 7
> CG321  CG311  NG311  CG311      2.5000  1   180.00 ! Pose , from NG311
> CG321 NG311 CG2R61, PENALTY= 117
> CG321  CG311  NG311  CG311      1.5000  2     0.00 ! Pose , from NG311
> CG321 NG311 CG2R61, PENALTY= 117
> CG321  CG311  NG311  CG311      0.5000  3     0.00 ! Pose , from NG311
> CG321 NG311 CG2R61, PENALTY= 117
> CG321  CG311  NG311  HGPAM1     0.1000  3     0.00 ! Pose , from CG331
> CG321 NG311 HGP1, PENALTY= 6.4
> HGA1   CG311  NG311  CG311      0.0000  3   180.00 ! Pose , from HGA2
> CG321 NG311 CG2R61, PENALTY= 77.5

Dihedrals clearly need work, though by fixing one or two things, you may 
dramatically bring down the penalties (and luckily the problems are largely from 
the same couple of terms, not like you have to parametrize a bunch of different 
dihedrals).  The target data here would be QM energy values at fixed 15-degree 
intervals of the target dihedrals, with everything else free to relax.  Since 
this is a ring system, a full scan of 360 degrees won't be possible, but +/- 90 
is a reasonable start.

-Justin

> HGA1   CG311  NG311  HGPAM1     0.0500  3     0.00 ! Pose , from HGA2
> CG321 NG311 HGPAM1, PENALTY= 4
> CG311  CG321  CG321  CG311      0.1950  3     0.00 ! PROT alkane
> update, adm jr., 3/2/92
> CG311  CG321  CG321  CG321      0.5000  3     0.00 ! CARBOCY carbocyclic sugars
> CG311  CG321  CG321  CG321      0.5000  6   180.00 ! CARBOCY carbocyclic sugars
> CG311  CG321  CG321  CG331      0.1505  2     0.00 ! Pose , from CG321
> CG321 CG321 CG331, PENALTY= 0.6
> CG311  CG321  CG321  CG331      0.0813  3   180.00 ! Pose , from CG321
> CG321 CG321 CG331, PENALTY= 0.6
> CG311  CG321  CG321  CG331      0.1082  4     0.00 ! Pose , from CG321
> CG321 CG321 CG331, PENALTY= 0.6
> CG311  CG321  CG321  CG331      0.2039  5     0.00 ! Pose , from CG321
> CG321 CG321 CG331, PENALTY= 0.6
> CG311  CG321  CG321  HGA2       0.1950  3     0.00 ! NA abasic nucleoside
> CG321  CG321  CG321  HGA2       0.1950  3     0.00 ! LIPID alkanes
> CG331  CG321  CG321  HGA2       0.1800  3     0.00 ! LIPID alkane
> HGA2   CG321  CG321  HGA2       0.2200  3     0.00 ! LIPID alkanes
> CG321  CG321  CG331  HGA3       0.1600  3     0.00 ! PROT rotation
> barrier in Ethane (SF)
> HGA2   CG321  CG331  HGA3       0.1600  3     0.00 ! PROT rotation
> barrier in Ethane (SF)
>
> IMPROPERS
>
> END
> RETURN
>
>
>
> On Sat, Mar 28, 2015 at 5:51 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>>
>> On 3/28/15 7:05 AM, Priya Das wrote:
>>
>>> I am sorry to bother again and again.  I am new to it and still learning
>>> the basics.
>>> My molecule is a decahydroquinoline. The paramchem generated .str file is
>>> HERE
>>> <https://cgenff.paramchem.org/initguess/filedownload.php?
>>> file=20150328/Pose1.str>
>>> .
>>>
>>
>> That file is not accessible.  I'm not sure why there are high penalties in
>> that molecule; it is very straightforward.
>>
>>   I am following CGennFF tutorial and your instructions as HERE
>>> <http://mackerell.umaryland.edu/~kenno/cgenff/program.html>. As penalties
>>> are there i need to use QM, but i am not able to run CHARMM simulations as
>>> CHARMM is not freely available. So tried to use this Toolkit
>>> <http://www.ks.uiuc.edu/Research/vmd/plugins/fftk/>, but still in vain.
>>>
>>>
>> Because neither CHARMM nor fftk do what you need to do.  You need QM
>> software that is capable of doing geometry optimizations, angle and
>> dihedral scans, and vibrational analysis.  We use Gaussian.  If you don't
>> have access to that kind of software, you're not going to be able to
>> generate the target data you need, simply put.
>>
>> On the MM side, assuming you can generate the QM target data for
>> refinement, any package will work - CHARMM, GROMACS, etc.  You don't
>> explicitly need CHARMM. You need something that can do energy minimization
>> and single-point energy evaluations.
>>
>>
>> -Justin
>>
>> --
>> ==================================================
>>
>> Justin A. Lemkul, Ph.D.
>> Ruth L. Kirschstein NRSA Postdoctoral Fellow
>>
>> Department of Pharmaceutical Sciences
>> School of Pharmacy
>> Health Sciences Facility II, Room 629
>> University of Maryland, Baltimore
>> 20 Penn St.
>> Baltimore, MD 21201
>>
>> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
>> http://mackerell.umaryland.edu/~jalemkul
>>
>> ==================================================
>> --
>> Gromacs Users mailing list
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>
>
>

-- 
==================================================

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==================================================


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