ProQDock

Requires PERL (v.5.8 or higher), and a fortran90 compiler (prefered: ifort) and six additional packages to be pre-installed

1. sc from ccp4 (http://www.ccp4.ac.uk/) [executable_name: sc]
2. delphi v.6.2 (http://compbio.clemson.edu/delphi) [executable_name: delphi95]
3. Rosetta (https://www.rosettacommons.org/software/)
4. ProQ2 (https://github.com/bjornwallner/ProQ_scripts/)
5. needle from EMBOS (http://emboss.sourceforge.net/download/)

Installation

$ git clone https://github.com/bjornwallner/ProQDock
$ cd ProQDock
$ chmod +x compileF
$ ./compileF <fortran90-compiler>  (Default: ifort)

open ProQDock in any text editor and change the fullpaths for the following fields according to your system:

• sc_path=/software/apps/ccp4/ccp4-6.5.0/ccp4-6.5/bin
• delphi_path=/home/x_sabas/bin
• rosetta_path=/proj/wallner/users/x_bjowa/github/Rosetta/main/source/bin
• rosetta_db=/proj/wallner/users/x_bjowa/github/Rosetta/main/database
• svm_path=/home/x_sabas/proj/svm_light
• ESpath=/home/x_sabas/proj/EDTSurf
• proqpath=/home/x_sabas/proj/BACKUP/ProQ_scripts/bin

The program has two mandatory inputs :

    1. The coordinate (PDB) file for the model
    2. The full-length target sequence

• The model must be a perfect or imperfect subset of the target sequence
• i.e., Any and all sub-sequence present in the model must be present in the tareget
• PDB file MUST contain corrdinates of geometrically fixed Hydrogen atoms
• preferably fixed by REDUCE v.2 or atleast compatible with the REDUCE format (http://kinemage.biochem.duke.edu/downloads/software/reduce/)

Preparatory Step:

The full length (FASTA) target sequence (one letter amino acid code followed by a header starting with >) should be prepared and provided alongside the coordinate (PDB) file for the model.

You can generate the fasta sequence by using:

$ ProQDock/EXEC/pdb2fasta.pl <input.pdb>  >  input.pdb.fasta

Run Step:

$ ProQDock/ProQDock <model.PDB> <fulllength.fasta>

where,

• model.pdb: The input pdb (coordinate file in Brrokheaven format; http://www.ccp4.ac.uk/html/procheck_man/manappb.html) file

• fulllength.fasta: The fulllength fasta sequence of the target

• optional arguments: -d (0/1) : delphi_mode:

       0: Single_internal_dielectric (epsilon=2) 
       1: Multidielctric mode (internal dielectric modeled as a Gaussian Function)

If you intend to Run ProQDock for a list of PDB files (models) corresponding to the same target sequence, then, SKIP repeating the profile generation step more than once, by providing a [consistent basename] for the fasta file.

Launch the following bash script which runs on a set of (example) models kept at ./EXAMPLE_CASE_STUDY/

$ ./runex.bash

EXAMPLE OUTPUT:

$ cat EXAMPLE_CASE_STUDY/D1OYV-models.status.results 

        Model         fnat       LRMS       iRMS     CAPRI_class    DockQ    ProQDock
     D1OYV-a102a      0.000     35.348     15.846     Incorrect    0.02118    0.05908
     D1OYV-a104c      0.000     44.703     16.626     Incorrect    0.01432    0.21024
     D1OYV-a106c      0.000     44.600     18.136     Incorrect    0.01395    0.03890
     D1OYV-a115c      0.000     31.946     11.941     Incorrect    0.02722    0.02730
      D1OYV-a61c      0.652      6.820      2.334    Acceptable    0.51761    0.51060
      D1OYV-a61d      0.630      6.574      2.450    Acceptable    0.50960    0.46046
      D1OYV-a81d      0.587      6.788      2.481    Acceptable    0.48841    0.42648
      D1OYV-a41b      0.717      3.619      1.428        Medium    0.69617    0.48751
      D1OYV-a62c      0.707      3.991      1.628        Medium    0.66168    0.55795
      D1OYV-a82d      0.707      4.347      1.593        Medium    0.65639    0.48664

Example Output for a single PDB file:

$ ./ProQDock ./TESTPDBS/1u07.pdb ./TEMP/1u07.pdb.fasta

The file has a Proper extension (.pdb / .PDB)
=============================================================
Normal Delphi (single internal dielectric, epsilon = 2.0) will be executed

Setting CCP4_SCR to /tmp/tmp.hAw2aARLGb/ccp4_scr!
Cleaning of the temp files in this
directory is not done automatically.

===========================================================
Total number of residues in the Complex: 178
=================================================================================================================================
Feature   Range  Direction  Description                                            Feature_Type   Stability* Native_values (DB3)
---------------------------------------------------------------------------------------------------------------------------------
EC:       [-1,1] Positive   Electrostatic balance at the interface                 Interface      Variable    0.20 (+/-0.38)
Sc:       [-1,1] Positive   Geometric / Steric fit at the interface                Interface       Stable     0.68 (+/-0.17)
rGb:      [-1,1] Positive   Distribution of hydrophobicity with respect to burial  All_Atom        Stable     0.06 (+/-0.02)
Ld:       [0, 1] Ambiguous  Link (packing) densely at the interface                Interface       Stable     0.15 (+/-0.17)
nBSA:     [0, 1] Ambiguous  Size of the interface relative to the whole complex    Interface      Variable    0.07 (+/-0.05)
Fintres:  [0, 1] Ambiguous  Size of the interface relative to the whole complex    Interface      Variable    0.19 (+/-0.13)
CPscore:  [0, 1] Positive   inter-residue contacts preference                      Interface      Variable    0.35 (+/-0.17)
CPM:      [0, 1] Positive   Likelihood of (Sc,EC) given nBSA compared to native    Interface      Variable    0.80 (+/-0.18)
rTs:      [0, 1] Negative   Energetic Stability of the whole molecule              All_Atom        Stable     0.22 (+/-0.21)
Isc:      [0, 1] Negative   Binding energy                                         Interface      Variable    0.20 (+/-0.33)
Erep:     [0, 1] Negative   Unfavourable Energy due to atomic Clashes              All_Atom        Stable     0.41 (+/-0.15)
Etmr:     [0, 1] Negative   Energetic Stability without condiderating clashes      All_Atom        Stable     0.28 (+/-0.16)
ProQ2:    [0, 1] Positive   Overall Structural Quality                             All_Atom       Variable    0.80 (+/-0.12)
---------------------------------------------------------------------------------------------------------------------------------
ProQDock  [0, 1] Positive   The predicted DockQ score, Basu and Wallner, 2016, https://doi.org/10.1371/journal.pone.0161879
   DockQ Statistics on CAPRI data:  
    0    <  DockQ <  0.23 - Incorrect
    0.23 <= DockQ <  0.49 - Acceptable quality
    0.49 <= DockQ <  0.80 - Medium quality
            DockQ >= 0.80 - High quality
=================================================================================================================================
EC=0.443
Sc=0.767
rGb=0.07170
Ld=0.14815
nBSA=0.115345
Fintres=0.286517
CPscore=0.490153
CPM=0.94593
rTs=0.04831
Isc=0.00000
Erep=0.34970
Etmr=0.09889
ProQ=0.845
================The ProQDock Score ====================
ProQDock:    1.10501
Features:  /tmp/x_bjowa/ProQDock/TESTPDB/1u07.SVMfeatures
ProQDock score:  /tmp/x_bjowa/lProQDock/TESTPDB/1u07.ProQDock
Raw Rosetta terms:  /tmp/x_bjowa/ProQDock/TESTPDB/1u07.Rterms

Reference

  Finding correct protein–protein docking models using ProQDock
  Sankar Basu and Björn Wallner* 
  Bioinformatics (2016) 32 (12): i262-i270. 
  doi: 10.1093/bioinformatics/btw257

The article is avialable online here: http://bioinformatics.oxfordjournals.org/content/32/12/i262.abstract