[gmx-users] Re: Carbohydrate simulation: problem with the terminal atoms

Justin A. Lemkul jalemkul at vt.edu
Mon Apr 2 15:58:11 CEST 2012



khuchtumur wrote:
> Hi Justin,
> 
> Thank you for writing this clarification. I'm still having a bit of a
> problem with the anomeric -OH group giving LINCS warnings during
> equilibration though. 
> 
> I am trying to parametrize a beta-lactose molecule in g53a6. Following are
> the steps I followed.
> 1) Draw lactose in Avogadro
> 2) Use PRODRG to get ITP template
> 3) Change the charges and charge groups in accordance with Oostenbrink et al
> 2004 and Lins et al 2005.
> 4) Change the bonds and angles in accordance with Oostenbrink et al, which
> matches Lins et al
> 5) Check the improper dihedrals for chiral centers
> 6) Set up the proper dihedrals using Lins et al. 
> 7) Set the exclusion you mentioned here (between O5 and H1)
> 8) Change the C-C-C-O5 specification from Lins et al to CCCO1 specification
> as in your post (explained below)
> 
> This gives the following charges and dihedrals:
> 
> [ atoms ]
> ;   nr      type  resnr resid  atom  cgnr   charge     mass
>      1        OA     1  LAT      O2     1   -0.642  15.9994   
>      2         H     1  LAT     H2     1    0.410   1.0080   
>      3       CH1     1  LAT      C2     1    0.232  13.0190   
>      4       CH1     1  LAT      C3     2    0.232  13.0190   
>      5        OA     1  LAT      O3     2   -0.642  15.9994   
>      6         H     1  LAT     H3     2    0.410   1.0080   
>      7       CH1     1  LAT      C4     3    0.232  13.0190   
>      8        OA     1  LAT      O4     3   -0.642  15.9994   
>      9         H     1  LAT     H4     3    0.410   1.0080   
>     10       CH1     1  LAT      C5     4    0.376  13.0190   
>     11       CH2     1  LAT      C6     5    0.232  14.0270   
>     12        OA     1  LAT      O6     5   -0.642  15.9994   
>     13         H     1  LAT     H6     5    0.410   1.0080   
>     14        OA     1  LAT      O5     4   -0.480  15.9994   
>     15       CH1     1  LAT      C1     4    0.232  13.0190   
>     16        OA     1  LAT      O1     4   -0.360  15.9994   
>     17       CH1     1  LAT     C4'     4    0.232  13.0190 ;'
>     18       CH1     1  LAT     C3'     6    0.232  13.0190 ;'
>     19        OA     1  LAT     O3'     6   -0.642  15.9994 ;'
>     20         H     1  LAT     H3'     6    0.410   1.0080   
>     21       CH1     1  LAT     C2'     7    0.232  13.0190 ;'
>     22        OA     1  LAT     O2'     7   -0.642  15.9994 ;'
>     23         H     1  LAT     H2'     7    0.410   1.0080   
>     24       CH1     1  LAT     C1'     8    0.232  13.0190 ;'
>     25        OA     1  LAT     O1'     8   -0.538  15.9994 ;'
>     26         H     1  LAT     H1'     8    0.410   1.0080   
>     27        OA     1  LAT     O5'     8   -0.480  15.9994 ;'
>     28       CH1     1  LAT     C5'     8    0.376  13.0190 ;'
>     29       CH2     1  LAT     C6'     9    0.232  14.0270 ;'
>     30        OA     1  LAT     O6'     9   -0.642  15.9994 ;'
>     31         H     1  LAT     H6'     9    0.410   1.0080   
> 
> [ dihedrals ]
> 
>    2   1   3  15   1      gd_30
> ;   2   1   3   4   1      gd_30
>    1   3  15  16   1      gd_18
> ;   1   3  15  14   1      gd_18
>    1   3   4   5   1      gd_18
>    1   3   4   7   1      gd_17
> ;   3  15  16  17   1      gd_29
>    3  15  14  10   1      gd_29
>    3   4   5   6   1      gd_30
>    3   4   7   8   1      gd_17
>    3   4   7  10   1      gd_34
>   15   3   4   7   1      gd_34
>   15   3   4   5   1      gd_17
>   16  15   3   4   1      gd_17
>   16  15   3   4   1      gd_34
>   14  15   3   4   1      gd_17
> ;  14  15   3   4   1      gd_34
> ;   6   5   4   7   1      gd_30
>    5   4   7   8   1      gd_18
>    5   4   7  10   1      gd_17
>    4   7   8   9   1      gd_30
>    4   7  10  11   1      gd_34
>    4   7  10  14   1      gd_17
> ;   4   7  10  14   1      gd_34
> ;   9   8   7  10   1      gd_30
>    8   7  10  11   1      gd_17
> ;   8   7  10  14   1      gd_18
> ;   7  10  11  12   1      gd_1
>    7  10  14  15   1      gd_29
>   13  12  11  10   1      gd_30
>   12  11  10  14   1      gd_3
>   12  11  10  14   1      gd_35
> ;  11  10  14  15   1      gd_29
>   14  15  16  17   1      gd_2
>   14  15  16  17   1      gd_32
>   15  16  17  18   1      gd_30
> ;  15  16  17  28   1      gd_29
>   16  17  18  19   1      gd_18
>   16  17  18  21   1      gd_17
>   16  17  28  29   1      gd_17
> ;  16  17  28  27   1      gd_18
> ;  17  18  19  20   1      gd_30
>   17  18  21  22   1      gd_17
>   17  18  21  24   1      gd_34
> ;  17  28  29  30   1      gd_17
>   17  28  27  24   1      gd_29
>   19  18  17  28   1      gd_17
>   18  17  28  29   1      gd_34
>   18  17  28  27   1      gd_17
> ;  18  17  28  27   1      gd_34
>   21  18  17  28   1      gd_34
>   20  19  18  21   1      gd_30
>   19  18  21  22   1      gd_18
>   19  18  21  24   1      gd_17
> ;  18  21  22  23   1      gd_30
>   18  21  24  25   1      gd_17
>   18  21  24  25   1      gd_34
>   18  21  24  27   1      gd_17
> ;  18  21  24  27   1      gd_34 
>   23  22  21  24   1      gd_30
>   22  21  24  25   1      gd_18
> ;  22  21  24  27   1      gd_18
> ;  21  24  25  26   1      gd_30
>   21  24  27  28   1      gd_29
>   26  25  24  27   1      gd_2
>   26  25  24  27   1      gd_32
> ;  26  25  24  27   1    180.0   20.0  1  ; restrain?  
> http://compbio.biosci.uq.edu.au/atb/download.py?molid=2002
> ;  24  27  28  29   1      gd_29
>   27  28  29  30   1      gd_5
>   27  28  29  30   1      gd_37
>   28  29  30  31   1      gd_30
> 
> ;  28  27  24  25   1     180.0  10.0   1
>   
> ; Picked from Autieri et al J. Chem. Phys. 2010
> ;  10   7   4   5   1     180.0   2.4   2
> ;  15   3   4   5   1     180.0   2.4   2
> ;   4   3  15  16   1     180.0   0.5   2
> ;  11  10  14  15   1     180.0   0.5   2
> ;   7   4   3   1   1     180.0   0.5   2
> ;  28  17  18  19   1     180.0   2.4   2
> ;  24  21  18  19   1     180.0   2.4   2
> ;  18  21  24  25   1     180.0   0.5   2
> ;  29  28  27  24   1     180.0   0.5   2 
> ;  17  18  21  22   1     180.0   0.5   2
> [ exclusions ]
>    26   27
> #The commented dihedrals are things I was trying#
> 
> The molecule starts giving off LINCS warnings during NVT or NPT
> equilibration with a protein that I'm interested in. I have run just the
> molecule alone to check if it's a problem with the complex, but the molecule
> in water also gives the same error. The error is on the anomeric hydroxy
> group on the reducing end of the molecule, namely glucose O1-H1. My
> questions are:
> 
> 1) In this post, you have set both gd_17 and gd_34 for C3-C2-C1-O1, while
> Lins et al 2005 have set up gd_17 and gd_34 for C3-C4-C5-O5 or C3-C2-C1-O5.
> My assumption is that Lins et al are treating the O5 as if it's a carbon
> within the sugar ring. My chemistry is not good, but the O5 here is quite
> different from that of the other oxygens and could require extra attention.

In the context of dihedrals, that's doubtful.  Maybe on some quantum level there 
is an important distinction, but not likely here.  Take that up with the authors 
of the force field itself ;)

> I'm not sure why the O1 is treated like this in your post. Is it because
> it's in a polymer? Also I noticed that you did not have the extra gd_34
> definition for the dihedrals involving the O5, was it left out on purpose? 

The building blocks I made were derived directly from what was available in the 
53A6 force field.  As I recall, everything else matched aside from what I added. 
  I'll leave that as an exercise to you to determine.  I did simple diagnostic 
simulations to verify stability, nothing more.

> 2) I realize that there are different ways to set the dihedrals for complete
> coverage of the molecule (i. e. C2-C3-O3-H3/C4-C3-O3-H3). Is there any down
> side to defining all of the possible dihedrals redundantly?

If you define multiple dihedrals for a given bond, they are summed together to 
give the final term.  Unless you have specific reason to do that, don't.

> 3) I realize that the topology you've shown here is a template, but have you
> simulated this template successfully?
> 

Yes.

> I have run 1'-deoxy-1'-methoxylactose (replacing the glucose OH with a
> terminal methoxy {according to the specifications from Lins et al} ) and it
> doesn't give LINCS warnings. I haven't made any quality checks, but this
> actually runs. So this simple change makes me think that the problem is not
> anything else but this anomeric OH termination. 
> Other notes: running gmx v4.5.5, spc water, em run until Fmax <100
> 
> I'm sorry if I rambled on. This is the first molecule I'm parameterizing.
> Please let me know if I made any careless mistakes or if there are other
> lit. articles I should have taken into account. 
> 

Why not try using ATB to build the topology?

http://compbio.biosci.uq.edu.au/atb/

I think the results should be vastly more reliable than trying to 
reverse-engineer a faulty PRODRG topology.  They also have a reasonably large 
database of building block molecules with which you can check your work.

-Justin

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

Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

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



More information about the gromacs.org_gmx-users mailing list