Merge pull request #1517 from haddocking/randorien

Enables separate control of molecules separation and random rotations

Author: amjjbonvin

CHANGELOG.md

@@ -1,5 +1,6 @@
 # Changelog
 
+- 2026-04-15: Implemented separate control of separation and randome rotations of molecules - Issue #1491
 - 2026-04-15: Solve bug related to workflow restarting without analysis folder - Issue #1518
 - 2026-04-14: Increase max number of timesteps in openmm module - BioExcel forum 6072
 - 2026-04-12: Add possibility to run MD (mdref, mdscoring) without solvent - Issue #1512

examples/docking-protein-glycan/docking-flexref-protein-glycan-full.cfg

@@ -35,7 +35,8 @@ tolerance = 5
 # generate 500 models 
 sampling_factor = 500
 # randomize starting orientations
-randorien = true
+randrot = true
+separate = true
 # increase the number of steps by a factor 10 to allow 
 # for docking during the flexible refinement
 mdsteps_rigid = 5000 

examples/docking-protein-glycan/docking-flexref-protein-glycan-test.cfg

@@ -30,7 +30,8 @@ tolerance = 20
 # generate 5 models 
 sampling_factor = 5
 # randomize starting orientations
-randorien = true
+randrot = true
+separate = true
 # increase the number of steps by a factor 10 to allow 
 # for docking during the flexible refinement
 mdsteps_rigid = 5000 

examples/docking-protein-ligand/data/neuraminidase-2BAT.pdb

@@ -0,0 +1,89 @@
+HETATM    1  C1  G39 B 500      -3.025  80.782 110.942  1.00 31.18      B    C  
+HETATM    2  O1A G39 B 500      -3.636  81.879 110.998  1.00 30.30      B    O  
+HETATM    3  O1B G39 B 500      -3.567  79.723 111.340  1.00 31.23      B    O  
+HETATM    4  C2  G39 B 500      -1.651  80.740 110.409  1.00 30.48      B    C  
+HETATM    5  C3  G39 B 500      -0.943  79.410 110.260  1.00 30.04      B    C  
+HETATM    6  C4  G39 B 500       0.093  79.431 109.132  1.00 30.37      B    C  
+HETATM    7  N4  G39 B 500       0.917  78.238 109.241  1.00 30.09      B    N1+
+HETATM    8  C5  G39 B 500       0.966  80.691 109.164  1.00 29.53      B    C  
+HETATM    9  N5  G39 B 500       1.947  80.677 108.092  1.00 28.16      B    N  
+HETATM   10  C6  G39 B 500       0.118  81.958 109.065  1.00 30.53      B    C  
+HETATM   11  C7  G39 B 500      -1.023  81.887 110.069  1.00 30.75      B    C  
+HETATM   12  O7  G39 B 500       0.919  83.133 109.320  1.00 31.80      B    O  
+HETATM   13  C8  G39 B 500       0.893  84.122 108.269  1.00 30.52      B    C  
+HETATM   14  C9  G39 B 500      -0.455  84.855 108.189  1.00 31.36      B    C  
+HETATM   15  C10 G39 B 500       3.265  80.575 108.300  1.00 27.13      B    C  
+HETATM   16  O10 G39 B 500       3.787  80.702 109.401  1.00 26.14      B    O  
+HETATM   17  C11 G39 B 500       4.088  80.286 107.080  1.00 26.05      B    C  
+HETATM   18  C81 G39 B 500       2.001  85.154 108.476  1.00 29.88      B    C  
+HETATM   19  C82 G39 B 500       3.389  84.594 108.252  1.00 28.23      B    C  
+HETATM   20  C91 G39 B 500      -0.795  85.628 109.453  1.00 32.33      B    C  
+HETATM   21  H01 G39 B 500       1.200  78.111 110.202  1.00 30.09      B    H  
+HETATM   22  H02 G39 B 500       0.124  85.973 109.928  1.00 32.33      B    H  
+HETATM   23  H03 G39 B 500      -1.684  78.639 110.045  1.00 30.04      B    H  
+HETATM   24  H04 G39 B 500      -0.435  79.444 108.178  1.00 30.37      B    H  
+HETATM   25  H05 G39 B 500       1.736  78.340 108.659  1.00 30.09      B    H  
+HETATM   26  H06 G39 B 500       1.488  80.695 110.120  1.00 29.53      B    H  
+HETATM   27  H07 G39 B 500       1.617  80.747 107.140  1.00 28.16      B    H  
+HETATM   28  H08 G39 B 500      -0.285  82.029 108.055  1.00 30.53      B    H  
+HETATM   29  H09 G39 B 500      -1.351  82.814 110.539  1.00 30.75      B    H  
+HETATM   30  H10 G39 B 500       1.049  83.584 107.334  1.00 30.52      B    H  
+HETATM   31  H11 G39 B 500      -1.239  84.120 108.011  1.00 31.36      B    H  
+HETATM   32  H12 G39 B 500       4.908  79.617 107.344  1.00 26.05      B    H  
+HETATM   33  H13 G39 B 500       1.939  85.529 109.498  1.00 29.88      B    H  
+HETATM   34  H14 G39 B 500       3.935  84.586 109.195  1.00 28.23      B    H  
+HETATM   35  H15 G39 B 500      -1.338  84.980 110.140  1.00 32.33      B    H  
+HETATM   36  H16 G39 B 500      -0.418  79.204 111.193  1.00 30.04      B    H  
+HETATM   37  H17 G39 B 500       0.387  77.434 108.937  1.00 30.09      B    H  
+HETATM   38  H18 G39 B 500      -0.379  85.580 107.379  1.00 31.36      B    H  
+HETATM   39  H19 G39 B 500       4.492  81.217 106.684  1.00 26.05      B    H  
+HETATM   40  H20 G39 B 500       1.848  85.944 107.741  1.00 29.88      B    H  
+HETATM   41  H21 G39 B 500       3.920  85.215 107.530  1.00 28.23      B    H  
+HETATM   42  H22 G39 B 500      -1.416  86.486 109.198  1.00 32.33      B    H  
+HETATM   43  H23 G39 B 500       3.462  79.811 106.324  1.00 26.05      B    H  
+HETATM   44  H24 G39 B 500       3.312  83.576 107.868  1.00 28.23      B    H  
+CONECT    1    2    3    4
+CONECT    2    1
+CONECT    3    1
+CONECT    4    1    5   11
+CONECT    5    4    6   23   36
+CONECT    6    5    7    8   24
+CONECT    7    6   21   25   37
+CONECT    8    6    9   10   26
+CONECT    9    8   15   27
+CONECT   10    8   11   12   28
+CONECT   11    4   10   29
+CONECT   12   10   13
+CONECT   13   12   14   18   30
+CONECT   14   13   20   31   38
+CONECT   15    9   16   17
+CONECT   16   15
+CONECT   17   15   32   39   43
+CONECT   18   13   19   33   40
+CONECT   19   18   34   41   44
+CONECT   20   14   22   35   42
+CONECT   21    7
+CONECT   22   20
+CONECT   23    5
+CONECT   24    6
+CONECT   25    7
+CONECT   26    8
+CONECT   27    9
+CONECT   28   10
+CONECT   29   11
+CONECT   30   13
+CONECT   31   14
+CONECT   32   17
+CONECT   33   18
+CONECT   34   19
+CONECT   35   20
+CONECT   36    5
+CONECT   37    7
+CONECT   38   14
+CONECT   39   17
+CONECT   40   18
+CONECT   41   19
+CONECT   42   20
+CONECT   43   17
+CONECT   44   19
+END

examples/docking-protein-ligand/data/oseltamivir_zwitterion-centered.pdb

@@ -0,0 +1,79 @@
+# ====================================================================
+# Protein-ligand docking example, where ligans is pre-placed ("centered") at the binding site 
+
+# directory in which the docking will be done
+run_dir = "run1-centered"
+
+# execution mode
+mode = "local"
+ncores = 50
+
+# molecules to be docked
+molecules =  [
+    "data/neuraminidase-2BAT.pdb",
+    "data/oseltamivir_zwitterion-centered.pdb"
+    ]
+
+# ====================================================================
+[topoaa]
+autohis = true
+ligand_param_fname = "data/ligand-prodrg.param"
+ligand_top_fname = "data/ligand-prodrg.top"
+delenph = false
+
+[rigidbody]
+tolerance = 5
+# Setting `separate = false` to keep the ligand in the binding site 
+separate = false
+mol_fix_origin_1 = true
+ambig_fname = "data/ambig-active-rigidbody.tbl"
+ligand_param_fname = "data/ligand-prodrg.param"
+ligand_top_fname = "data/ligand-prodrg.top"
+sampling = 1000
+w_vdw = 0.0
+inter_rigid = 0.001
+
+[caprieval]
+reference_fname = "data/target.pdb"
+
+[seletop]
+select = 200
+
+[caprieval]
+reference_fname = "data/target.pdb"
+
+[flexref]
+tolerance = 5
+ambig_fname = "data/ambig-passive.tbl"
+ligand_param_fname = "data/ligand-prodrg.param"
+ligand_top_fname = "data/ligand-prodrg.top"
+mdsteps_rigid = 0
+mdsteps_cool1 = 0
+
+[caprieval]
+reference_fname = "data/target.pdb"
+
+[ilrmsdmatrix]
+
+[clustrmsd]
+criterion = 'distance'
+linkage = 'average'
+min_population = 4
+clust_cutoff = 1.5
+
+[seletopclusts]
+top_models = 4
+
+[caprieval]
+reference_fname = "data/target.pdb"
+
+# Running final caprieval with allatoms parameter set to true to also
+#  include the evaluation of protein side chains
+#  in both the alignment process and irmsd, ilrmsd computations
+# NOTE that all ligand atoms are always considered even without this option.
+[caprieval]
+allatoms = true
+reference_fname = "data/target.pdb"
+
+# ====================================================================
+

examples/docking-protein-ligand/docking-protein-ligand-centered-full.cfg

@@ -0,0 +1,79 @@
+# ====================================================================
+# Protein-ligand docking example, where ligans is pre-placed ("cenetered") at the binding site 
+
+# directory in which the docking will be done
+run_dir = "run1-centered-test"
+
+# execution mode
+mode = "local"
+ncores = 50
+
+# molecules to be docked
+molecules =  [
+    "data/neuraminidase-2BAT.pdb",
+    "data/oseltamivir_zwitterion-centered.pdb"
+    ]
+
+# ====================================================================
+[topoaa]
+autohis = true
+ligand_param_fname = "data/ligand-prodrg.param"
+ligand_top_fname = "data/ligand-prodrg.top"
+delenph = false
+
+[rigidbody]
+tolerance = 5
+# Setting `separate = false` to keep the ligand in the binding site 
+separate = false
+mol_fix_origin_1 = true
+ambig_fname = "data/ambig-active-rigidbody.tbl"
+ligand_param_fname = "data/ligand-prodrg.param"
+ligand_top_fname = "data/ligand-prodrg.top"
+sampling = 20
+w_vdw = 0.0
+inter_rigid = 0.001
+
+[caprieval]
+reference_fname = "data/target.pdb"
+
+[seletop]
+select = 5
+
+[caprieval]
+reference_fname = "data/target.pdb"
+
+[flexref]
+tolerance = 5
+ambig_fname = "data/ambig-passive.tbl"
+ligand_param_fname = "data/ligand-prodrg.param"
+ligand_top_fname = "data/ligand-prodrg.top"
+mdsteps_rigid = 0
+mdsteps_cool1 = 0
+
+[caprieval]
+reference_fname = "data/target.pdb"
+
+[ilrmsdmatrix]
+
+[clustrmsd]
+criterion = 'distance'
+linkage = 'average'
+min_population = 1
+clust_cutoff = 1.5
+
+[seletopclusts]
+top_models = 4
+
+[caprieval]
+reference_fname = "data/target.pdb"
+
+# Running final caprieval with allatoms parameter set to true to also
+#  include the evaluation of protein side chains
+#  in both the alignment process and irmsd, ilrmsd computations
+# NOTE that all ligand atoms are always considered even without this option.
+[caprieval]
+allatoms = true
+reference_fname = "data/target.pdb"
+
+# ====================================================================
+

examples/docking-protein-ligand/docking-protein-ligand-centered-test.cfg

@@ -22,7 +22,8 @@ end if
 ! Initialisation of variables
 !==================================================================!
 
-evaluate ($saprotocol.randorien=$randorien)
+evaluate ($saprotocol.randrot=$randrot)
+evaluate ($saprotocol.separate=$separate)
 evaluate ($saprotocol.tadhigh_t=$temp_high)
 evaluate ($saprotocol.t1_init=$temp_cool1_init)
 evaluate ($saprotocol.t2_init=$temp_cool2_init)
@@ -227,8 +228,10 @@ if ($select gt 0) then
 end if
 
 ! random placement of molecules
-if ($SaProtocol.randorien eq true) then
+if ($SaProtocol.separate eq true) then
     @MODULE:separate.cns
+end if
+if ($SaProtocol.randrot eq true) then
     @MODULE:random_rotations.cns
 end if