python script results in unexpected very negative affinity score
gkxiao opened this issue · comments
I believe this to be a bug with Vina 1.2
Environment Information
Vina: 1.2.3
OS: Centos 7.6
Data set: https://github.com/gkxiao/very-negative-vina-score
Expected Behavior
pose_1.pdbqt is a docking pose from a command line calculation, the expected affinity score is -7.925 as following:
from vina import Vina
#create docking object
receptor = 'receptor.pdbqt'
ligand = 'pose_1.pdbqt'
output = 'pose_1_out.pdbqt'
dock = Vina(sf_name='vina',seed=-1280817548,verbosity=2)
dock.set_receptor(receptor)
center = [5.061, 2.751, 17.703]
box_size = [15, 15, 15]
dock.compute_vina_maps(center=center, box_size=box_size)
dock.set_ligand_from_file(ligand)
#dock.dock()
energy = dock.score()
print('Score before minimization: %.3f (kcal/mol)' % energy[0])Score before minimization: -7.925 (kcal/mol)
Vina Binary version gives the same results.
vina_1.2 --config docking.conf --ligand pose_1.pdbqt --score_only --verbosity 2#################################################################
# If you used AutoDock Vina in your work, please cite: #
# #
# O. Trott, A. J. Olson, #
# AutoDock Vina: improving the speed and accuracy of docking #
# with a new scoring function, efficient optimization and #
# multithreading, Journal of Computational Chemistry 31 (2010) #
# 455-461 #
# #
# DOI 10.1002/jcc.21334 #
# #
# Please see http://vina.scripps.edu for more information. #
#################################################################
Scoring function : vina
Rigid receptor: receptor.pdbqt
Ligand: pose_1.pdbqt
Center: X 5.061 Y 2.751 Z 17.703
Size: X 15 Y 15 Z 15
Grid space: 0.375
Exhaustiveness: 8
CPU: 0
Verbosity: 2
Computing Vina grid ... done.
Estimated Free Energy of Binding : -7.925 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -10.241 (kcal/mol)
Ligand - Receptor : -10.241 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -0.693 (kcal/mol)
Ligand : -0.693 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 2.316 (kcal/mol)
(4) Unbound System's Energy : -0.693 (kcal/mol)Actual Behavior
Howerver, the python script in cammond line gives total differnt results: -149kcal/mol:
python docking.pyComputing Vina grid ... done.
WARNING: At low exhaustiveness, it may be impossible to utilize all CPUs.
Performing docking (random seed: -1280817548) ...
0% 10 20 30 40 50 60 70 80 90 100%
|----|----|----|----|----|----|----|----|----|----|
***************************************************
done.
ENERGY FROM SEARCH: -10.9406
FINAL ENERGY:
Estimated Free Energy of Binding : -149.841 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -10.251 (kcal/mol)
Ligand - Receptor : -10.251 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -0.689 (kcal/mol)
Ligand : -0.689 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 43.799 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -10.619
FINAL ENERGY:
Estimated Free Energy of Binding : -149.589 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -10.422 (kcal/mol)
Ligand - Receptor : -10.422 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -0.192 (kcal/mol)
Ligand : -0.192 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 43.725 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -9.823
FINAL ENERGY:
Estimated Free Energy of Binding : -148.981 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -8.748 (kcal/mol)
Ligand - Receptor : -8.748 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -1.080 (kcal/mol)
Ligand : -1.080 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 43.547 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -9.808
FINAL ENERGY:
Estimated Free Energy of Binding : -148.968 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -9.376 (kcal/mol)
Ligand - Receptor : -9.376 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -0.435 (kcal/mol)
Ligand : -0.435 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 43.543 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -9.693
FINAL ENERGY:
Estimated Free Energy of Binding : -148.878 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -8.934 (kcal/mol)
Ligand - Receptor : -8.934 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -0.762 (kcal/mol)
Ligand : -0.762 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 43.517 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -9.053
FINAL ENERGY:
Estimated Free Energy of Binding : -148.377 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -8.214 (kcal/mol)
Ligand - Receptor : -8.214 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -0.834 (kcal/mol)
Ligand : -0.834 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 43.371 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -9.180
FINAL ENERGY:
Estimated Free Energy of Binding : -148.483 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -9.501 (kcal/mol)
Ligand - Receptor : -9.501 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : 0.316 (kcal/mol)
Ligand : 0.316 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 43.402 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -8.835
FINAL ENERGY:
Estimated Free Energy of Binding : -148.213 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -8.022 (kcal/mol)
Ligand - Receptor : -8.022 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -0.813 (kcal/mol)
Ligand : -0.813 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 43.323 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -8.624
FINAL ENERGY:
Estimated Free Energy of Binding : -148.057 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -8.141 (kcal/mol)
Ligand - Receptor : -8.141 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -0.493 (kcal/mol)
Ligand : -0.493 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 43.277 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -8.157
FINAL ENERGY:
Estimated Free Energy of Binding : -147.690 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -7.094 (kcal/mol)
Ligand - Receptor : -7.094 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -1.066 (kcal/mol)
Ligand : -1.066 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 43.170 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -8.324
FINAL ENERGY:
Estimated Free Energy of Binding : -138.088 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : 4.966 (kcal/mol)
Ligand - Receptor : 4.966 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -0.718 (kcal/mol)
Ligand : -0.718 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 40.363 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -8.091
FINAL ENERGY:
Estimated Free Energy of Binding : -141.540 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : 0.372 (kcal/mol)
Ligand - Receptor : 0.372 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -0.584 (kcal/mol)
Ligand : -0.584 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 41.372 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -8.126
FINAL ENERGY:
Estimated Free Energy of Binding : -147.664 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -7.620 (kcal/mol)
Ligand - Receptor : -7.620 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -0.507 (kcal/mol)
Ligand : -0.507 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 43.162 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -6.997
FINAL ENERGY:
Estimated Free Energy of Binding : -146.795 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -8.043 (kcal/mol)
Ligand - Receptor : -8.043 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : 1.040 (kcal/mol)
Ligand : 1.040 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 42.908 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -5.683
FINAL ENERGY:
Estimated Free Energy of Binding : -145.777 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -4.769 (kcal/mol)
Ligand - Receptor : -4.769 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -0.919 (kcal/mol)
Ligand : -0.919 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 42.611 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -5.912
FINAL ENERGY:
Estimated Free Energy of Binding : -135.714 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : 7.984 (kcal/mol)
Ligand - Receptor : 7.984 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -0.667 (kcal/mol)
Ligand : -0.667 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 39.669 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -5.692
FINAL ENERGY:
Estimated Free Energy of Binding : -143.846 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -4.257 (kcal/mol)
Ligand - Receptor : -4.257 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : 1.065 (kcal/mol)
Ligand : 1.065 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 42.046 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -5.537
FINAL ENERGY:
Estimated Free Energy of Binding : -145.661 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : -4.676 (kcal/mol)
Ligand - Receptor : -4.676 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -0.863 (kcal/mol)
Ligand : -0.863 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 42.577 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: -5.444
FINAL ENERGY:
Estimated Free Energy of Binding : -141.908 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : 0.098 (kcal/mol)
Ligand - Receptor : 0.098 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : -0.785 (kcal/mol)
Ligand : -0.785 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : 41.480 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
ENERGY FROM SEARCH: 247.478
FINAL ENERGY:
Estimated Free Energy of Binding : 50.180 (kcal/mol) [=(1)+(2)+(3)+(4)]
(1) Final Intermolecular Energy : 64.848 (kcal/mol)
Ligand - Receptor : 64.848 (kcal/mol)
Ligand - Flex side chains : 0.000 (kcal/mol)
(2) Final Total Internal Energy : 182.700 (kcal/mol)
Ligand : 182.700 (kcal/mol)
Flex - Receptor : 0.000 (kcal/mol)
Flex - Flex side chains : 0.000 (kcal/mol)
(3) Torsional Free Energy : -14.668 (kcal/mol)
(4) Unbound System's Energy : 182.700 (kcal/mol)
mode | affinity | dist from best mode
| (kcal/mol) | rmsd l.b.| rmsd u.b.
-----+------------+----------+----------
1 -149.8414 0.0000 0.0000
2 -149.5893 0.7274 2.3684
3 -148.9809 3.2994 6.4348
4 -148.9676 1.8543 3.0350
5 -148.8782 1.8490 2.8579
6 -148.4830 2.4573 3.6517
7 -148.3769 3.8287 7.5138
8 -148.2126 3.8224 7.4557
9 -148.0573 2.2618 3.7545
10 -147.6903 3.6454 6.9867
11 -147.6641 1.5086 2.4942
12 -146.7947 1.8645 2.2871
13 -145.7771 2.9325 6.8320
14 -145.6614 3.3765 7.2577
15 -143.8460 3.3936 4.4782
16 -141.9077 2.0037 3.0612
17 -141.5400 1.9712 3.4042
18 -138.0882 1.6318 2.4177
19 -135.7138 3.4993 7.2856
20 50.1802 6.6452 8.4232Obviously, Very high term 3 and 4 results in the very negative affinity score. By the way, the actual affinity is (1)+(2)+(3)-(4) instead of (1)+(2)+(3)+(4).
Steps to Reproduce
The materials to reproduce the results can be available from: https://github.com/gkxiao/very-negative-vina-score
Thanks for the report and for the steps to reproduce. I can reproduce on CentOS.