Flexible Induced-fit Backbone Refinement in Molecular Docking

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Input Fields

There are two options for running the FireDock server:

  • Option 1 (use transformation file)
    • Receptor Molecule: PDB id and chain/s of the receptor (pdb:chain, e.g. 1ukr:A) or a file containing the structure of the receptor in PDB format. Each residue of the receptor must have a unique number and chain.
      The user can choose whether he wants to model backbone movements of the receptor or not (model only side-chain refinement and minimization of the rigid body orientation).

    • Ligand Molecule: PDB id and chain/s of the ligand (pdb:chain, e.g. 1t6g:B) or a file containing the structure of the ligand in PDB format. Each residue of the receptor must have a unique number and chain.
      The user can choose whether he wants to model backbone movements of the ligand or not (model only side-chain refinement and minimization of the rigid body orientation).
      We recommend defining the smaller protein as the ligand, for better rigid-body minimization

      IMPORTANT! please use standard PDB atom naming in the files you upload!

    • Rigid Docking Solutions: The server accepts two file formats of rigid docking solutions
      • PatchDock transformations file (see example).
        It is a file containing the ligand's transformations in the following format:
        index X-rotation Y-rotation Z-rotation X-translation Y-translation Z-translation

        The rotation is around the X, Y and Z axes (in this order), and the angles are in radians.
        The translation parameters describe the movement of all the atoms of the ligand in the directions of the axes (X, Y and Z respectively) in Angstrom units.

        For example:
        1 2.11363 0.153389 2.82412 10.8802 -4.53751 -7.76723
        2 1.3353 -0.0999924 -2.60445 44.0002 4.52072 8.73591
        3 1.99255 0.159889 2.81949 12.0745 -2.47299 -9.35544
        4 1.3353 -0.0999924 -2.49973 43.5566 7.54644 8.73591
        5 1.32362 0.0314778 -2.64412 42.0512 3.61016 5.47968

      • ZDOCK output file (see example).

      * Users can use any other rigid-docking method and prepare a transformation file according to the detailed PatchDock format.

      * The server can process up to 100 transformations. Therefore, the output files of PatchDock/ZDOCK must be trunked to contain only the first 1-100 best solutions for further flexible refinement.

  • Option 2 (use model file)
    • Models File: (see example)
      A file containing up to 100 models of complexes for refinement in PDB format (the backbone conformation of the proteins must be the same in all the models) and the chains of the receptor and the ligand.

  • e-mail address: An e-mail address for receiving the link to the results page. The results page will be available for at least a week.
Advanced Input Fields

Setting these parameters is optional:
  • Perform SCO for: Unchecking the boxes will keep side-chains of the molecule fixed

  • SCO Level: Restricted or Full.
    The restricted refinement mode allows only the clashing residues to be flexible. The full refinement mode allows all the interface residues to be flexible and uses an extended rotamer library. We recommend using the restricted mode at first, for coarse refinement, and on the final best candidates to use the full mode.

  • Number of normal modes: The maximal number of low frequency normal modes that the program will use in the refinement. This parameter determined the amount of degrees of freedom of the backbone conformation, that the program will take into account during the refinement. However, the lower this value is, the faster the program will run. For example, if this parameter is set to 50, the program will refine the structure of the receptor by the most relevant normal modes among the 50 lowest frequency modes.

  • Backbone flexibility level: This parameter determines the restriction of the backbone conformational change. The lower it is, the more it prevents the backbone conformation to deform. The flexibility level must be between 0 and 1.

  • Number of MC Cycles: The number of Monte-Carlo cycles for the rigid body optimization.

  • Complex type: The type of the complex (Default, Antibody-Antigen or Enzyme-Inhibitor).
    This information is used for adjusting the scoring function.

  • Atomic radius scale: Must be between 0 and 1. Affects the Van der Waals energy component in the scoring function. A low number allows a certain amount of clashes between the atoms. We recommend using 0.8 for coarse refinement and 0.85 for a final refinement of the best candidates.


see output example below:

The output is a table of all the input solutions, ranked by the global energy value. The refined complex structure is generated for all the solutions. The user can view the complexes in the Jmol applet window and/or download the structures. The table can be sorted according to different properties:
  • Rank - according to the global energy.
  • Solution Number - according to the order of the transformations.
  • Global Energy - The binding energy of the solution.
  • Attractive and Repulsive VdW - The contribution of the van der Waals forces to the global binding energy.
  • ACE - The contribution of the atomic contact energy (ACE) to the global binding energy.
  • HB - The contribution of the hydrogen bonds to the global binding energy.

A more detailed table which contains all the energy terms of the solutions can be downloaded from the results page.
Among others, the table includes the linear combination of normal modes which creates the minimized structure of the proteins.
For example:-1.45*V1-1.00*V29 means that the structure is created by applying mode number 1 with an amplitude of -1.45 and mode number 29 with an amplitude of -1.00.
If the Normal Modes columns are empty, no backbone movement was modeled.

The results page will be available for at least a week.
Output example:
Receptor Ligand TransFile User e-mail
1ukrA.pdb 1t6gB.pdb 1t6g_trans.txt efratmas@gmail.com

Rank Solution Number Global Energy
Attractive VdW Repulsive VdW ACE HB Structure show/hide
1 1 -68.94   -42.97     27.76      -4.62   -2.59  
2 2 -60.15   -38.63     22.99      -5.28   -2.89  
3 6 -43.79   -41.38     48.63      -1.74   -3.64  
4 4 -34.34   -29.23     20.96      0.75   -0.93  
5 8 -28.33   -28.77     14.08      4.31   0.00  
6 7 -14.83   -21.94     10.55      0.07   -0.57  
7 3 -6.71   -21.60     12.67      7.20   -1.67  
8 10 -6.17   -32.76     26.24      4.15   -1.77  
9 9 -5.22   -30.99     23.13      5.63   -2.02  
10 5 -0.12   -30.15     17.70      0.98   -2.02  
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