GetAtoms

The program GetAtoms allow to model spatial protein structure by homology. The model of the target protein structure is built using homologous template protein structure and pairwise sequence alignment of the template and target proteins. The program allows to:

The program allows to input alignment data in various formats. The model output can be performed in PDB or AMBER formats.

For example, if we have 4hhb (A) sequence as query and 1hba(B) as template, simple format:


      VLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDL------SHGSAQVKGHGKKVAD
      HLTPEEKSAVTALWGKV--NVDEVGGEALGRLLVVYPRTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLG

      ALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTPAVHASLDKFLASVST
      AFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVAN

      VLTSKYR
      ALAHKYH

Program is provided with viewer.

The approach is shown in the Fig.1.

Fig.1. The approach of the GetAtoms program.

The program work in three stages.

First, the program makes side chain substitution in the template structure according to amino acid sequence in the target structure. Then rough preliminary side chain optimization is performed to remove steric clashes. The optimization is performed by Monte-Carlo algorithm a nd is as follows. Initially the side chain is placed in most frequent rotameric state. Then program searches for the side chains that form clashes and try to change their conformation randomly. If the sterical energy is lower than the energy at the previous step, new configuration is accepted. If not, the energy change dE is calculated and the value of exp(-dE/Temperature) is compared to the random number rand in the range [0,1]. If rand value is lower, such conformation is accepted. The Temperature specifies the temperature for MC algorithm of side chain conformation optimization, the lower the temperature, the faster is the convergence to the nearest local minima. Higher temperature allows overcoming local minima but needing more time for search. This procedure is repeated user-defined maximal number of MC steps (for the preliminary optimization the number of 50-100 for this parameter is recommended). Sometimes the side chain rotamer configuration can be trapped in the state with high sterical energy, to overcome this, it is useful to make restart from random configuration of rotamers to new optimal configuration if optimization is not successful in 100 steps. The restart is controlled by MC process restart option.

Second step performs main chain reconstruction in the insertion and deletion regions of the template-target superposition (Fig. 2).

Fig 2. The insertion modeling approach.

During insertion modeling the program try to generate many loop main chain conformation in attempt to "close" the space gap between the C-terminus of the loop and N-terminus of the residue immediately following after the insertion. These conformations are generated by Monte Carlo procedure and controlled by temperature and maximal number of iteration steps as described previously. Conformations that have the distance between loop C-termini modeled N-atom and the true anchor N-atom less then user-defined threshold (C-ter attachment criterion) then screened for the conformation that have minimal sterical energy of interaction with the other part of the protein. Note, that the two template residues immediately at the place of the insertion are "melted" (actually they are added to the loop) to make local distortion in the template to allow loop to be inserted.

The same procedure is implemented for deletions modeling (Fig 3).

Fig 3. The deletion modeling approach.

In this case two residues from both termini of the deletion are "melted" (actually they are formed a loop from 4 residues), that is build by previous algorithm.

After the insertion and deletion modeling the final optimization step is performed for side chain conformations only. The algorithm is the same as for the first step, but it is recommended to make the number of optimization steps larger (200-400).

The user can also control additional input and output parameters.

Alignment format: format of the alignment file. Several options are possible. "LOCAL", the output format of the Softberry FOLD program; "FASTA", FASTA-format; "SIMPLE", format with only sequences in the data (no sequence names); "CE", alignment format from the CE structural alignment program. First sequence is the target, second sequence is template. Columns of alignment containing only gaps in both sequences are ignored.

Adding Hydrogen atoms {ON,OFF}: the coordinates of the hydrogen atoms will be added to heavy atoms in the modeled structure.

StatusFile : the name of the file for calculation status output.

The output file contains some information about the optimization parameters and initial and final energy of the protein structure.

GetAtoms output:


      HEADER    OXYGEN TRANSPORT                        07-MAR-84   4HHB    
      REMARK  50
      REMARK  50 GETATOMS [ver=0.9.0.0; date=20020312]
      REMARK  50 Modelled from template structure provided by user.
      REMARK  50 Calculation parameters:
      REMARK  50   Simulated Annealing Temperature=2.000000
      REMARK  50   Simulated Annealing Maximal number of steps=100
      REMARK  50   Simulated Annealing steps done=-1073216864
      REMARK  50   Add Hydrogen Atoms=OFF
      REMARK  50 Final score data:
      REMARK  50   VDW_Score=1.089206e-19
      REMARK  50   Steric_Score=2.652495e-315
      REMARK  50   Bump_Score=0.000000e+00
      ATOM      1  N   VAL     1       9.223 -20.614   1.365
      ATOM      2  CA  VAL     1       8.694 -20.026  -0.123
      ATOM      3  C   VAL     1       9.668 -21.068  -1.645
      ATOM      4  O   VAL     1       9.370 -22.612  -0.994
      ATOM      5  CB  VAL     1       8.948 -18.511  -0.251
      ATOM      6  CG1 VAL     1       8.554 -18.010  -1.636
      ATOM      7  CG2 VAL     1       8.176 -17.751   0.822
      ATOM      8  N   LEU     2       9.270 -20.650  -2.180
      ATOM      9  CA  LEU     2      10.245 -21.378  -3.143
      ATOM     10  C   LEU     2      11.419 -20.331  -4.099
      ATOM     11  O   LEU     2      11.252 -19.250  -5.024
      ATOM     12  CB  LEU     2       9.461 -22.198  -4.174
      ATOM     13  CG  LEU     2       8.651 -23.375  -3.627
      ATOM     14  CD1 LEU     2       7.843 -24.024  -4.741
      ATOM     15  CD2 LEU     2       9.576 -24.392  -2.976
      ATOM     16  N   SER     3      12.365 -20.722  -3.649
      ATOM     17  CA  SER     3      13.611 -20.183  -4.477
      ATOM     18  C   SER     3      14.557 -21.356  -5.125
      ATOM     19  O   SER     3      14.340 -22.536  -4.780
      ATOM     20  CB  SER     3      14.497 -19.299  -3.595
      ATOM     21  OG  SER     3      15.076 -20.068  -2.554

      or  WITH H-atoms:

      REMARK  50   Add Hydrogen Atoms=ON
      REMARK  50 Final score data:
      REMARK  50   VDW_Score=1.089206e-19
      REMARK  50   Steric_Score=2.652495e-315
      REMARK  50   Bump_Score=0.000000e+00
      ATOM      1  N   VAL     1       9.223 -20.614   1.365
      ATOM      2  CA  VAL     1       8.694 -20.026  -0.123
      ATOM      3  C   VAL     1       9.668 -21.068  -1.645
      ATOM      4  O   VAL     1       9.370 -22.612  -0.994
      ATOM      5  CB  VAL     1       8.948 -18.511  -0.251
      ATOM      6  CG1 VAL     1       8.554 -18.010  -1.636
      ATOM      7  CG2 VAL     1       8.176 -17.751   0.822
      ATOM      8 1H   VAL     1      10.102 -20.497   1.435
      ATOM      9 2H   VAL     1       8.812 -20.175   2.021
      ATOM     10 3H   VAL     1       9.034 -21.482   1.426
      ATOM     11  HA  VAL     1       9.166 -20.592  -0.926
      ATOM     12  HB  VAL     1      10.006 -18.305  -0.091
      ATOM     13 1HG1 VAL     1       9.071 -17.073  -1.845
      ATOM     14 2HG1 VAL     1       8.833 -18.752  -2.384
      ATOM     15 3HG1 VAL     1       7.477 -17.846  -1.671
      ATOM     16 1HG2 VAL     1       7.168 -17.540   0.463
      ATOM     17 2HG2 VAL     1       8.120 -18.356   1.727
      ATOM     18 3HG2 VAL     1       8.686 -16.814   1.043
      ATOM     19  N   LEU     2       9.270 -20.650  -2.180
      ATOM     20  CA  LEU     2      10.245 -21.378  -3.143
      ATOM     21  C   LEU     2      11.419 -20.331  -4.099
      ATOM     22  O   LEU     2      11.252 -19.250  -5.024
      ATOM     23  CB  LEU     2       9.461 -22.198  -4.174
      ATOM     24  CG  LEU     2       8.651 -23.375  -3.627
      ATOM     25  CD1 LEU     2       7.843 -24.024  -4.741
      ATOM     26  CD2 LEU     2       9.576 -24.392  -2.976
      ATOM     27  H   LEU     2       8.525 -20.036  -1.884
      ATOM     28  HA  LEU     2      10.867 -22.070  -2.576
      ATOM     29 1HB  LEU     2       8.746 -21.553  -4.685
      ATOM     30 2HB  LEU     2      10.152 -22.623  -4.903
      ATOM     31  HG  LEU     2       7.969 -23.019  -2.854
      ATOM     32 1HD1 LEU     2       7.705 -23.310  -5.553
      ATOM     33 2HD1 LEU     2       8.376 -24.899  -5.114
      ATOM     34 3HD1 LEU     2       6.870 -24.328  -4.356
      ATOM     35 1HG2 LEU     2       9.162 -24.699  -2.016
      ATOM     36 2HG2 LEU     2       9.673 -25.263  -3.625
      ATOM     37 3HG2 LEU     2      10.558 -23.944  -2.822