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Re: "STARTING_MODEL" and"ENDING_MODEL"



Dear Dr. Zhang,

I believe it is not necessarily a good idea to use modeller for a heptapeptide
modeling based on another heptapeptide unless you are sure that they adopt a
very similar conformation.  I do not know what is your environment (is it a
docked peptide on a protein surface, or is it in solvent etc.) but there is no
guarantee that even the same heptapeptide will have the same conformation in
different environments.

Modeller relies on utilising the idea of evolution, that full size,
sequentially   similar proteins in physiological environment (for which
modeller basically does not account for) adopt similar folds, while small
peptides rely more on energetic criteria, which is not what modeller was
designed for.

Nevertheless:

> I also noticed that the backbone conformation of the model and the template is
> different. This is what I would like to overcome if possible. Probably I missed
> something in my top file if modeller can do this kind of work. Here is my top
> file.

Modeller builds a model based on the given restraints derived from statistical
observations of features from other proteins,  from molecular mechanics
forcefields and your template. These retrains  will not necessarily  guide the
model to entirely the same conformation as the  template. As i checked your
model and template I would say that is pretty much what one would expect.

As I mentioned above, in case of such a short fragment one is fairly lost,
having no solid reference, and  maybe way off reality.

If you want to force  modeling to deal only with sidechains and retain the same
backbone conformation include in your top file:

SUBROUTINE ROUTINE = 'select_atoms'
  PICK_ATOMS SELECTION_SEGMENT='@:@' 'X:X',;
   SELECTION_SEARCH='segment', PICK_ATOMS_SET=1, ;
   RES_TYPES='all', ATOM_TYPES='SDCH', ;
   SELECTION_FROM='all', SELECTION_STATUS='initialize'
  RETURN
END_SUBROUTINE


but I mention again that to my opinion it is an inadequate use of Modeller. I
would prefer some detailed mol mechanics or semi empirical  forcefields as
CHARMM, AMBER or ECEPP, preferably with solvent representation and exhaustive
optimisation method.

Sincerely,
Andras Fiser

> 
> # Homology modelling by the MODELLER TOP routine 'model'.
> 
> INCLUDE                                                  # Include the predefined
> TOP routines
> SET OUTPUT_CONTROL= 1 1 1 1
> SET ALNFILE  = 'peptide_1.ali'             # alignment filename
> SET KNOWNS   = '1dkxB'                     # codes of the templates
> SET SEQUENCE = 'peptide_1'              # code of the target
> SET ATOM_FILES_DIRECTORY = './:../atom_files'   # directories for input atom
> fileSET STARTING_MODEL= 1                           # index of the first model
> SET ENDING_MODEL  = 1                    # index of the last model
>                                                                     # (determines
> how many models to calculate)
> 
> CALL ROUTINE = 'model'                      # do homology modelling
> 
> SET FINAL_MALIGN3D = 1
> 
> And I also attached the model and template.
> 
> Thank you for your time.
> 
> Sincerely,
> 
> Xiao-Ping Zhang
> 
> Andras Fiser wrote:
> 
> > Hi
> >
> > STARTING and ENDING model variables define how many models to generate. Because
> > the structure optimization is stochastic  (MD simulation) you can expect minor
> > differences among different structures, especially if you have such regions in
> > the structure which are not very well defined by restraints (segments with
> > insertions, vicinity of deletions or  loosely defined substrates  relative to
> > the template etc.).
> >
> > These variables also define the extension of your model files as it was noted
> > by Azat: technically it is useful if you run modeling under  different
> > circumstances, e.g. generate 10 models with one ligand between 1-10, than
> > generate 10 models using different ligand or templates (Starting MODEL=11,
> > ENDING_MODEL=20) etc.
> >
> > > I am modeling a very short peptide with modeller4. If I set
> > > STARTING_MODEL=1, ENDING_MODEL=10, I get 10 models which have different
> > > orientations and spatial location. If I would like to get a model which
> > > can overlap with the original model (maximum uses the template
> > > coordinates), how to do it? And is it possible to keep the backbone  in
> > > the same conformation of original peptide ?
> >
> > if you include in your top file:
> > SET FINAL_MALIGN3D = 1
> >
> > modeller will automatically superpose all your models onto the template and
> > generate the *fit files which contains strcutures whith supeprosed coordinates.
> >
> > or you can write a short top script to superpose any number of structures from
> > any sources generated, as explained in the manual under MALIGN3D and  SUPERPOSE
> > commands.
> >
> > Andras
> >
> > --
> >     ,
> > Andras Fiser, PhD            # phone: (212) 327 7206
> > The Rockefeller University   # fax:   (212) 327 7540
> > Box 270, 1230 York Avenue    # e-mail:
> > New York, NY 10021-6399, USA # http://salilab.org/~andras
> 
> ******************************
> Xiao-Ping Zhang
> Department of Biochemistry
> Arrhenius Laboratories of Natural Sciences
> Stockholm Universities
> 106 91 Stockholm
> Sweden
> 
> Phone:  046-08-162472 /162582
> Fax:    046-08-153679
> e-mail: 
> 
>   -------------------------------------------------------------------------------
> ATOM   1666  N   ASN B   1      50.702  87.722  38.867  1.00 43.10           N
> ATOM   1667  CA  ASN B   1      51.449  86.814  37.946  1.00 41.67           C
> ATOM   1668  C   ASN B   1      51.328  87.331  36.498  1.00 39.68           C
> ATOM   1669  O   ASN B   1      50.267  87.216  35.865  1.00 39.73           O
> ATOM   1670  CB  ASN B   1      50.874  85.389  38.031  1.00 44.13           C
> ATOM   1671  CG  ASN B   1      50.750  84.878  39.468  1.00 46.27           C
> ATOM   1672  OD1 ASN B   1      50.338  85.626  40.353  1.00 46.16           O
> ATOM   1673  ND2 ASN B   1      51.084  83.634  39.757  1.00 45.47           N
> ATOM   1674  N   ARG B   2      52.433  87.895  36.025  1.00 36.65           N
> ATOM   1675  CA  ARG B   2      52.555  88.448  34.656  1.00 32.06           C
> ATOM   1676  C   ARG B   2      53.586  87.620  33.873  1.00 28.54           C
> ATOM   1677  O   ARG B   2      54.665  87.294  34.387  1.00 25.94           O
> ATOM   1678  CB  ARG B   2      53.006  89.911  34.728  1.00 36.71           C
> ATOM   1679  CG  ARG B   2      52.282  90.816  33.727  1.00 41.73           C
> ATOM   1680  CD  ARG B   2      50.777  90.927  33.989  1.00 44.15           C
> ATOM   1681  NE  ARG B   2      50.050  91.548  32.870  1.00 47.60           N
> ATOM   1682  CZ  ARG B   2      48.751  91.877  32.904  1.00 47.23           C
> ATOM   1683  NH1 ARG B   2      48.009  91.654  33.997  1.00 49.83           N
> ATOM   1684  NH2 ARG B   2      48.094  92.442  31.880  1.00 44.33           N
> ATOM   1685  N   LEU B   3      53.236  87.297  32.635  1.00 25.64           N
> ATOM   1686  CA  LEU B   3      54.079  86.438  31.778  1.00 22.32           C
> ATOM   1687  C   LEU B   3      54.737  87.207  30.621  1.00 22.74           C
> ATOM   1688  O   LEU B   3      54.225  88.243  30.169  1.00 22.20           O
> ATOM   1689  CB  LEU B   3      53.235  85.323  31.158  1.00 18.68           C
> ATOM   1690  CG  LEU B   3      52.213  84.739  32.134  1.00 19.46           C
> ATOM   1691  CD1 LEU B   3      51.449  83.546  31.556  1.00 20.46           C
> ATOM   1692  CD2 LEU B   3      52.846  84.236  33.433  1.00 15.12           C
> ATOM   1693  N   LEU B   4      55.858  86.627  30.205  1.00 20.92           N
> ATOM   1694  CA  LEU B   4      56.688  87.110  29.086  1.00 23.64           C
> ATOM   1695  C   LEU B   4      56.790  86.014  28.021  1.00 27.49           C
> ATOM   1696  O   LEU B   4      56.680  84.818  28.324  1.00 28.91           O
> ATOM   1697  CB  LEU B   4      58.117  87.414  29.559  1.00 25.41           C
> ATOM   1698  CG  LEU B   4      58.192  88.438  30.690  1.00 24.73           C
> ATOM   1699  CD1 LEU B   4      59.616  88.631  31.223  1.00 24.26           C
> ATOM   1700  CD2 LEU B   4      57.716  89.830  30.272  1.00 24.71           C
> ATOM   1701  N   LEU B   5      57.000  86.447  26.792  1.00 29.48           N
> ATOM   1702  CA  LEU B   5      57.145  85.533  25.643  1.00 30.37           C
> ATOM   1703  C   LEU B   5      58.628  85.360  25.284  1.00 31.29           C
> ATOM   1704  O   LEU B   5      59.481  86.132  25.727  1.00 27.62           O
> ATOM   1705  CB  LEU B   5      56.468  86.114  24.395  1.00 32.09           C
> ATOM   1706  CG  LEU B   5      55.053  86.640  24.629  1.00 35.07           C
> ATOM   1707  CD1 LEU B   5      54.403  87.181  23.350  1.00 40.10           C
> ATOM   1708  CD2 LEU B   5      54.100  85.569  25.156  1.00 38.35           C
> ATOM   1709  N   THR B   6      58.897  84.333  24.478  1.00 36.46           N
> ATOM   1710  CA  THR B   6      60.264  84.053  23.927  1.00 44.50           C
> ATOM   1711  C   THR B   6      60.360  84.677  22.466  1.00 47.61           C
> ATOM   1712  O   THR B   6      59.699  84.184  21.554  1.00 48.64           O
> ATOM   1713  CB  THR B   6      60.477  82.528  23.817  1.00 47.63           C
> ATOM   1714  OG1 THR B   6      59.676  81.818  24.755  1.00 53.22           O
> ATOM   1715  CG2 THR B   6      61.928  82.107  24.047  1.00 48.63           C
> ATOM   1716  N   GLY B   7      61.232  85.767  22.212  1.00 50.38           N
> ATOM   1717  CA  GLY B   7      61.334  86.583  20.844  1.00 51.64           C
> ATOM   1718  C   GLY B   7      62.588  86.267  20.033  1.00 53.33           C
> ATOM   1719  O   GLY B   7      63.180  85.187  20.170  1.00 53.27           O
> ATOM   1720  OXT GLY B   7      62.917  87.254  19.203  1.00 53.00           O
> 
>   -------------------------------------------------------------------------------
> REMARK Produced by MODELLER:  unknown   unknown                                1
> ATOM   1666  N   ASN B   1      50.702  87.722  38.867  1.00 43.10           N
> ATOM   1667  CA  ASN B   1      51.449  86.814  37.946  1.00 41.67           C
> ATOM   1668  C   ASN B   1      51.328  87.331  36.498  1.00 39.68           C
> ATOM   1669  O   ASN B   1      50.267  87.216  35.865  1.00 39.73           O
> ATOM   1670  CB  ASN B   1      50.874  85.389  38.031  1.00 44.13           C
> ATOM   1671  CG  ASN B   1      50.750  84.878  39.468  1.00 46.27           C
> ATOM   1672  OD1 ASN B   1      50.338  85.626  40.353  1.00 46.16           O
> ATOM   1673  ND2 ASN B   1      51.084  83.634  39.757  1.00 45.47           N
> ATOM   1674  N   ARG B   2      52.433  87.895  36.025  1.00 36.65           N
> ATOM   1675  CA  ARG B   2      52.555  88.448  34.656  1.00 32.06           C
> ATOM   1676  C   ARG B   2      53.586  87.620  33.873  1.00 28.54           C
> ATOM   1677  O   ARG B   2      54.665  87.294  34.387  1.00 25.94           O
> ATOM   1678  CB  ARG B   2      53.006  89.911  34.728  1.00 36.71           C
> ATOM   1679  CG  ARG B   2      52.282  90.816  33.727  1.00 41.73           C
> ATOM   1680  CD  ARG B   2      50.777  90.927  33.989  1.00 44.15           C
> ATOM   1681  NE  ARG B   2      50.050  91.548  32.870  1.00 47.60           N
> ATOM   1682  CZ  ARG B   2      48.751  91.877  32.904  1.00 47.23           C
> ATOM   1683  NH1 ARG B   2      48.009  91.654  33.997  1.00 49.83           N
> ATOM   1684  NH2 ARG B   2      48.094  92.442  31.880  1.00 44.33           N
> ATOM   1685  N   LEU B   3      53.236  87.297  32.635  1.00 25.64           N
> ATOM   1686  CA  LEU B   3      54.079  86.438  31.778  1.00 22.32           C
> ATOM   1687  C   LEU B   3      54.737  87.207  30.621  1.00 22.74           C
> ATOM   1688  O   LEU B   3      54.225  88.243  30.169  1.00 22.20           O
> ATOM   1689  CB  LEU B   3      53.235  85.323  31.158  1.00 18.68           C
> ATOM   1690  CG  LEU B   3      52.213  84.739  32.134  1.00 19.46           C
> ATOM   1691  CD1 LEU B   3      51.449  83.546  31.556  1.00 20.46           C
> ATOM   1692  CD2 LEU B   3      52.846  84.236  33.433  1.00 15.12           C
> ATOM   1693  N   LEU B   4      55.858  86.627  30.205  1.00 20.92           N
> ATOM   1694  CA  LEU B   4      56.688  87.110  29.086  1.00 23.64           C
> ATOM   1695  C   LEU B   4      56.790  86.014  28.021  1.00 27.49           C
> ATOM   1696  O   LEU B   4      56.680  84.818  28.324  1.00 28.91           O
> ATOM   1697  CB  LEU B   4      58.117  87.414  29.559  1.00 25.41           C
> ATOM   1698  CG  LEU B   4      58.192  88.438  30.690  1.00 24.73           C
> ATOM   1699  CD1 LEU B   4      59.616  88.631  31.223  1.00 24.26           C
> ATOM   1700  CD2 LEU B   4      57.716  89.830  30.272  1.00 24.71           C
> ATOM   1701  N   LEU B   5      57.000  86.447  26.792  1.00 29.48           N
> ATOM   1702  CA  LEU B   5      57.145  85.533  25.643  1.00 30.37           C
> ATOM   1703  C   LEU B   5      58.628  85.360  25.284  1.00 31.29           C
> ATOM   1704  O   LEU B   5      59.481  86.132  25.727  1.00 27.62           O
> ATOM   1705  CB  LEU B   5      56.468  86.114  24.395  1.00 32.09           C
> ATOM   1706  CG  LEU B   5      55.053  86.640  24.629  1.00 35.07           C
> ATOM   1707  CD1 LEU B   5      54.403  87.181  23.350  1.00 40.10           C
> ATOM   1708  CD2 LEU B   5      54.100  85.569  25.156  1.00 38.35           C
> ATOM   1709  N   THR B   6      58.897  84.333  24.478  1.00 36.46           N
> ATOM   1710  CA  THR B   6      60.264  84.053  23.927  1.00 44.50           C
> ATOM   1711  C   THR B   6      60.360  84.677  22.466  1.00 47.61           C
> ATOM   1712  O   THR B   6      59.699  84.184  21.554  1.00 48.64           O
> ATOM   1713  CB  THR B   6      60.477  82.528  23.817  1.00 47.63           C
> ATOM   1714  OG1 THR B   6      59.676  81.818  24.755  1.00 53.22           O
> ATOM   1715  CG2 THR B   6      61.928  82.107  24.047  1.00 48.63           C
> ATOM   1716  N   GLY B   7      61.232  85.767  22.212  1.00 50.38           N
> ATOM   1717  CA  GLY B   7      61.334  86.583  20.844  1.00 51.64           C
> ATOM   1718  C   GLY B   7      62.588  86.267  20.033  1.00 53.33           C
> ATOM   1719  O   GLY B   7      63.180  85.187  20.170  1.00 53.27           O
> ATOM   1720  OXT GLY B   7      62.917  87.254  19.203  1.00 53.00           O
> 
>   -------------------------------------------------------------------------------
> REMARK Produced by MODELLER:  unknown   unknown                                1
> REMARK Produced by MODELLER:  unknown   unknown                                1
> REMARK MODELLER OBJECTIVE FUNCTION:        26.9688
> ATOM      1  N   LEU     1      55.010  84.333  35.414  1.00   .65       1SG   2
> ATOM      2  CA  LEU     1      53.968  85.226  35.960  1.00   .65       1SG   3
> ATOM      3  CB  LEU     1      54.576  86.546  36.460  1.00   .65       1SG   4
> ATOM      4  CG  LEU     1      55.517  86.395  37.669  1.00   .65       1SG   5
> ATOM      5  CD2 LEU     1      55.807  87.761  38.311  1.00   .65       1SG   6
> ATOM      6  CD1 LEU     1      56.797  85.616  37.318  1.00   .65       1SG   7
> ATOM      7  C   LEU     1      52.984  85.564  34.899  1.00   .65       1SG   8
> ATOM      8  O   LEU     1      52.463  84.686  34.216  1.00   .65       1SG   9
> ATOM      9  N   ARG     2      52.699  86.870  34.759  1.00   .93       1SG  10
> ATOM     10  CA  ARG     2      51.769  87.286  33.762  1.00   .93       1SG  11
> ATOM     11  CB  ARG     2      51.341  88.752  33.924  1.00   .93       1SG  12
> ATOM     12  CG  ARG     2      49.987  89.081  33.293  1.00   .93       1SG  13
> ATOM     13  CD  ARG     2      48.810  88.536  34.111  1.00   .93       1SG  14
> ATOM     14  NE  ARG     2      48.986  89.024  35.510  1.00   .93       1SG  15
> ATOM     15  CZ  ARG     2      48.532  90.257  35.886  1.00   .93       1SG  16
> ATOM     16  NH1 ARG     2      47.868  91.051  34.997  1.00   .93       1SG  17
> ATOM     17  NH2 ARG     2      48.729  90.696  37.163  1.00   .93       1SG  18
> ATOM     18  C   ARG     2      52.490  87.139  32.464  1.00   .93       1SG  19
> ATOM     19  O   ARG     2      53.008  86.065  32.159  1.00   .93       1SG  20
> ATOM     20  N   ARG     3      52.564  88.223  31.668  1.00   .88       1SG  21
> ATOM     21  CA  ARG     3      53.229  88.095  30.409  1.00   .88       1SG  22
> ATOM     22  CB  ARG     3      52.989  89.248  29.411  1.00   .88       1SG  23
> ATOM     23  CG  ARG     3      53.492  90.618  29.887  1.00   .88       1SG  24
> ATOM     24  CD  ARG     3      53.730  91.607  28.738  1.00   .88       1SG  25
> ATOM     25  NE  ARG     3      52.428  92.217  28.346  1.00   .88       1SG  26
> ATOM     26  CZ  ARG     3      52.025  93.407  28.885  1.00   .88       1SG  27
> ATOM     27  NH1 ARG     3      52.803  94.045  29.807  1.00   .88       1SG  28
> ATOM     28  NH2 ARG     3      50.851  93.977  28.488  1.00   .88       1SG  29
> ATOM     29  C   ARG     3      54.698  88.058  30.662  1.00   .88       1SG  30
> ATOM     30  O   ARG     3      55.161  88.076  31.802  1.00   .88       1SG  31
> ATOM     31  N   ALA     4      55.461  87.968  29.562  1.00   .49       1SG  32
> ATOM     32  CA  ALA     4      56.886  87.958  29.616  1.00   .49       1SG  33
> ATOM     33  CB  ALA     4      57.464  86.858  30.523  1.00   .49       1SG  34
> ATOM     34  C   ALA     4      57.312  87.656  28.224  1.00   .49       1SG  35
> ATOM     35  O   ALA     4      56.570  87.027  27.470  1.00   .49       1SG  36
> ATOM     36  N   SER     5      58.516  88.102  27.828  1.00   .41       1SG  37
> ATOM     37  CA  SER     5      58.909  87.798  26.491  1.00   .41       1SG  38
> ATOM     38  CB  SER     5      59.982  88.738  25.914  1.00   .41       1SG  39
> ATOM     39  OG  SER     5      59.411  90.008  25.645  1.00   .41       1SG  40
> ATOM     40  C   SER     5      59.458  86.415  26.493  1.00   .41       1SG  41
> ATOM     41  O   SER     5      60.492  86.133  27.098  1.00   .41       1SG  42
> ATOM     42  N   LEU     6      58.736  85.510  25.810  1.00   .40       1SG  43
> ATOM     43  CA  LEU     6      59.134  84.144  25.669  1.00   .40       1SG  44
> ATOM     44  CB  LEU     6      57.933  83.183  25.626  1.00   .40       1SG  45
> ATOM     45  CG  LEU     6      57.147  83.103  26.955  1.00   .40       1SG  46
> ATOM     46  CD2 LEU     6      58.071  82.759  28.139  1.00   .40       1SG  47
> ATOM     47  CD1 LEU     6      55.963  82.127  26.846  1.00   .40       1SG  48
> ATOM     48  C   LEU     6      59.804  84.111  24.339  1.00   .40       1SG  49
> ATOM     49  O   LEU     6      60.999  83.838  24.235  1.00   .40       1SG  50
> ATOM     50  N   GLY     7      59.034  84.403  23.277  1.00   .24       1SG  51
> ATOM     51  CA  GLY     7      59.619  84.472  21.974  1.00   .24       1SG  52
> ATOM     52  C   GLY     7      59.258  83.201  21.229  1.00   .24       1SG  53
> ATOM     53  O   GLY     7      58.244  82.561  21.606  1.00   .24       1SG  54
> ATOM     54  OXT GLY     7      59.994  82.858  20.266  1.00   .24       1SG  55
> END

-- 
    ,
Andras Fiser, PhD            # phone: (212) 327 7206
The Rockefeller University   # fax:   (212) 327 7540 
Box 270, 1230 York Avenue    # e-mail:
New York, NY 10021-6399, USA # http://salilab.org/~andras