[Dock-fans] use_clash_overlap and use_internal_energy
Jerry Parks
jmp17 at duke.edu
Thu Jun 12 14:49:56 PDT 2008
John
It definitely helps get reduce clashes if I increase clash_overlap from
0.5 to 1.0, but I still get some pretty close contacts. I guess I would
just expect a value of 1.0 to eliminate *all* vdw clashes/overlaps.
I've attached a couple of mol2 files that demonstrate the results.
Thanks,
Jerry
On Thu, 12 Jun 2008, John J. Irwin wrote:
> Hi Jerry
>
> In an email in dock-fans dated Mon Jul 24 12:07:30 2006, Kaushik
> suggests setting clash_overlap to a bigger number, maybe 1.0. I see you
> had it at 0.5. So, would you try 1.0 and let us know if that solves the
> problem? I do agree you should not see major clashes in docking output.
>
> Hope this helps
>
> John
>
>
>
>
>
> Jerry Parks wrote:
> > John
> >
> > All the results I mentioned in my previous email were obtained with DOCK
> > v6.2.
> >
> > You have a good point about just buying the compounds, but apparently our
> > experimental collaborators want to make at least some of them on their
> > own. I guess it's good synthesis practice for the grad students.
> >
> > So, do you see any obvious input file errors that could be fixed so that
> > we get more realistic geometries? Would we need to use AMBER Score to
> > prevent the intramolecular ligand clashes?
> >
> > Thanks,
> > Jerry
> >
> > On Wed, 11 Jun 2008, John J. Irwin wrote:
> >
> >
> >> Hi Jerry
> >>
> >> Are you using the latest version, DOCK 6.2 ?
> >>
> >> I hope you will not have to synthesize compounds, but just buy them.
> >> That is the whole point of ZINC - to shorten the hypothesis-test cycle.
> >>
> >> Good luck.
> >>
> >> John
> >>
> >>
> >> Jerry Parks wrote:
> >>
> >>> Hello
> >>>
> >>> We have been using anchor-and-grow to perform flexible docking and
> >>> minimization on a large number of compounds from the zinc7 database. Many
> >>> of the highest scoring compounds suffer from geometries with unreasonable,
> >>> overlapping functional groups and rings. I really don't think we can trust
> >>> the results we've obtained thus far.
> >>>
> >>> Our goal is to generate leads via docking, then synthesize approximately
> >>> 20-50 molecules and assay them to determine if they are in fact
> >>> inhibitors.
> >>>
> >>> I have seen previous posts regarding "interpenetrated" structures, etc.,
> >>> but I'm still not sure how to circumvent this problem. It seems to me that
> >>> use_internal_energy should prevent these types of overlaps if the
> >>> repulsive vdw exponent is in effect. Any help/advice would be appreciated.
> >>>
> >>> I have attached a representative input file below.
> >>>
> >>> Thanks,
> >>> Jerry
> >>>
> >>> --------------------
> >>>
> >>> ligand_atom_file test-8.mol2
> >>> limit_max_ligands no
> >>> skip_molecule no
> >>> read_mol_solvation no
> >>> calculate_rmsd no
> >>> orient_ligand yes
> >>> automated_matching yes
> >>> receptor_site_file ../selected_spheres.sph
> >>> max_orientations 500
> >>> critical_points no
> >>> chemical_matching no
> >>> use_ligand_spheres no
> >>> flexible_ligand yes
> >>> min_anchor_size 40
> >>> pruning_use_clustering yes
> >>> pruning_max_orients 100
> >>> pruning_clustering_cutoff 100
> >>> use_internal_energy yes
> >>> internal_energy_att_exp 6
> >>> internal_energy_rep_exp 12
> >>> internal_energy_dielectric 4.0
> >>> use_clash_overlap yes
> >>> clash_overlap 0.50
> >>> bump_filter no
> >>> score_molecules yes
> >>> contact_score_primary no
> >>> contact_score_secondary no
> >>> grid_score_primary yes
> >>> grid_score_secondary no
> >>> grid_score_rep_rad_scale 1
> >>> grid_score_vdw_scale 1
> >>> grid_score_es_scale 1
> >>> grid_score_grid_prefix ../grid_999_10
> >>> dock3.5_score_secondary no
> >>> continuous_score_secondary no
> >>> gbsa_zou_score_secondary no
> >>> gbsa_hawkins_score_secondary no
> >>> amber_score_secondary no
> >>> minimize_ligand yes
> >>> minimize_anchor yes
> >>> minimize_flexible_growth yes
> >>> use_advanced_simplex_parameters no
> >>> simplex_max_cycles 1
> >>> simplex_score_converge 0.1
> >>> simplex_cycle_converge 1.0
> >>> simplex_trans_step 1.0
> >>> simplex_rot_step 0.1
> >>> simplex_tors_step 10.0
> >>> simplex_anchor_max_iterations 500
> >>> simplex_grow_max_iterations 500
> >>> simplex_final_min no
> >>> simplex_random_seed 0
> >>> atom_model all
> >>> vdw_defn_file ../vdw_AMBER_parm99.defn
> >>> flex_defn_file ../flex.defn
> >>> flex_drive_file ../flex_drive.tbl
> >>> ligand_outfile_prefix test-8
> >>> write_orientations no
> >>> num_scored_conformers_written 1
> >>> rank_ligands yes
> >>> max_ranked_ligands 500
> >>>
> >>> _______________________________________________
> >>> Dock-fans mailing list
> >>> Dock-fans at docking.org
> >>> http://blur.compbio.ucsf.edu/mailman/listinfo/dock-fans
> >>>
> >>>
>
-------------- next part --------------
@<TRIPOS>MOLECULE
ZINC04262355
66 68 1 0 0
SMALL
GASTEIGER
Energy = 0
@<TRIPOS>ATOM
1 C1 4.6226 10.0775 37.0776 C.3 1 <0>1 -0.1764
2 C2 5.7125 9.8751 36.0232 C.3 1 <0>1 0.1342
3 C3 5.1604 10.2367 34.6429 C.3 1 <0>1 -0.1375
4 C4 6.1595 8.4117 36.0264 C.3 1 <0>1 -0.1902
5 O1 6.8469 10.7282 36.3298 O.3 1 <0>1 -0.3277
6 C5 8.0020 10.4621 35.6914 C.2 1 <0>1 0.6728
7 O2 8.7278 9.5743 36.0934 O.2 1 <0>1 -0.5889
8 N1 8.3535 11.1802 34.6066 N.am 1 <0>1 -0.5349
9 N2 9.1921 10.6410 33.6728 N.3 1 <0>1 -0.2646
10 C6 8.5193 10.5109 32.3735 C.3 1 <0>1 0.0573
11 C7 8.9229 9.2108 31.7268 C.ar 1 <0>1 -0.0619
12 C8 7.9549 8.3133 31.3163 C.ar 1 <0>1 -0.0856
13 C9 8.3249 7.1232 30.7183 C.ar 1 <0>1 -0.1258
14 C10 9.6631 6.8256 30.5407 C.ar 1 <0>1 -0.1252
15 C11 10.6310 7.7205 30.9566 C.ar 1 <0>1 -0.1230
16 C12 10.2610 8.9131 31.5494 C.ar 1 <0>1 -0.1032
17 C13 10.4234 11.4330 33.5510 C.3 1 <0>1 0.0294
18 H1 10.1925 12.4883 33.6975 H 1 <0>1 0.0993
19 C14 11.0242 11.2310 32.1586 C.3 1 <0>1 -0.0520
20 C15 10.6826 9.8507 31.6594 C.ar 1 <0>1 -0.0916
21 C16 9.3963 9.3642 31.8017 C.ar 1 <0>1 -0.0470
22 C17 9.0791 8.1013 31.3399 C.ar 1 <0>1 -0.2049
23 C18 10.0554 7.3169 30.7432 C.ar 1 <0>1 0.1124
24 C19 11.3468 7.8053 30.6067 C.ar 1 <0>1 -0.1530
25 C20 11.6574 9.0708 31.0650 C.ar 1 <0>1 -0.0793
26 O3 9.7472 6.0724 30.2927 O.3 1 <0>1 -0.3133
27 C21 8.3657 5.7074 30.2892 C.3 1 <0>1 0.1028
28 C22 8.1171 4.6712 31.3548 C.ar 1 <0>1 -0.0908
29 C23 7.6036 5.0501 32.5810 C.ar 1 <0>1 -0.0953
30 C24 7.3708 4.0989 33.5566 C.ar 1 <0>1 -0.1240
31 C25 7.6615 2.7702 33.3099 C.ar 1 <0>1 -0.1137
32 C26 8.1803 2.3920 32.0857 C.ar 1 <0>1 -0.1244
33 C27 8.4079 3.3424 31.1081 C.ar 1 <0>1 -0.0964
34 C28 11.4137 10.9858 34.5952 C.2 1 <0>1 0.4450
35 O4 12.5993 11.0814 34.3834 O.co2 1 <0>1 -0.6356
36 H2 4.2572 11.1034 37.0301 H 1 <0>1 0.0626
37 H3 3.7992 9.3895 36.8860 H 1 <0>1 0.0586
38 H4 5.0347 9.8842 38.0681 H 1 <0>1 0.0798
39 H5 5.9060 10.0068 33.8818 H 1 <0>1 0.0613
40 H6 4.2555 9.6602 34.4510 H 1 <0>1 0.0706
41 H7 4.9265 11.3009 34.6126 H 1 <0>1 0.0661
42 H8 6.5528 8.1541 37.0096 H 1 <0>1 0.0945
43 H9 5.3080 7.7713 35.7964 H 1 <0>1 0.0611
44 H10 6.9360 8.2674 35.2752 H 1 <0>1 0.0554
45 H11 8.0110 12.0801 34.4888 H 1 <0>1 0.4210
46 H12 7.4393 10.5235 32.5207 H 1 <0>1 0.0793
47 H13 8.8081 11.3419 31.7299 H 1 <0>1 0.0838
48 H14 6.9096 8.5438 31.4590 H 1 <0>1 0.1176
49 H15 7.5685 6.4242 30.3932 H 1 <0>1 0.1129
50 H16 9.9523 5.8941 30.0770 H 1 <0>1 0.1118
51 H17 11.6768 7.4880 30.8179 H 1 <0>1 0.1132
52 H18 11.0174 9.6125 31.8741 H 1 <0>1 0.1172
53 H19 10.6161 11.9758 31.4752 H 1 <0>1 0.0870
54 H20 12.1073 11.3407 32.2108 H 1 <0>1 0.0639
55 H21 8.6377 9.9736 32.2702 H 1 <0>1 0.1215
56 H22 8.0731 7.7234 31.4473 H 1 <0>1 0.1184
57 H23 12.1085 7.1965 30.1421 H 1 <0>1 0.1223
58 H24 12.6625 9.4516 30.9588 H 1 <0>1 0.1267
59 H25 7.7566 6.5887 30.4903 H 1 <0>1 0.0676
60 H26 8.1006 5.2972 29.3147 H 1 <0>1 0.0697
61 H27 7.3807 6.0888 32.7754 H 1 <0>1 0.1247
62 H28 6.9652 4.3942 34.5129 H 1 <0>1 0.1239
63 H29 7.4832 2.0274 34.0733 H 1 <0>1 0.1221
64 H30 8.4076 1.3539 31.8930 H 1 <0>1 0.1235
65 H31 8.8133 3.0469 30.1516 H 1 <0>1 0.1239
66 O5 10.9786 10.4811 35.7604 O.co2 1 <0>1 -0.7493
@<TRIPOS>BOND
1 1 2 1
2 1 36 1
3 1 37 1
4 1 38 1
5 2 3 1
6 2 4 1
7 2 5 1
8 3 39 1
9 3 40 1
10 3 41 1
11 4 42 1
12 4 43 1
13 4 44 1
14 5 6 1
15 6 7 2
16 6 8 am
17 8 9 1
18 8 45 1
19 9 10 1
20 9 17 1
21 10 11 1
22 10 46 1
23 10 47 1
24 11 16 ar
25 11 12 ar
26 12 13 ar
27 12 48 1
28 13 14 ar
29 13 49 1
30 14 15 ar
31 14 50 1
32 15 16 ar
33 15 51 1
34 16 52 1
35 17 18 1
36 17 19 1
37 17 34 1
38 19 20 1
39 19 53 1
40 19 54 1
41 20 25 ar
42 20 21 ar
43 21 22 ar
44 21 55 1
45 22 23 ar
46 22 56 1
47 23 24 ar
48 23 26 1
49 24 25 ar
50 24 57 1
51 25 58 1
52 26 27 1
53 27 28 1
54 27 59 1
55 27 60 1
56 28 33 ar
57 28 29 ar
58 29 30 ar
59 29 61 1
60 30 31 ar
61 30 62 1
62 31 32 ar
63 31 63 1
64 32 33 ar
65 32 64 1
66 33 65 1
67 34 35 ar
68 34 66 ar
@<TRIPOS>SUBSTRUCTURE
1 <0>1 1 TEMP 0 **** **** 0 ROOT
########## Name: ZINC04474014
########## Grid Score: -58.060341
########## vdw: -47.305569
########## es: -10.754770
-------------- next part --------------
########## Name: ZINC04262355
########## Grid Score: -62.366383
########## vdw: -49.247429
########## es: -13.118955
@<TRIPOS>MOLECULE
ZINC04262355
66 68 1 0 0
SMALL
GASTEIGER
Energy = 0
@<TRIPOS>ATOM
1 C1 5.6032 1.4944 37.1217 C.3 1 <0>1 -0.1764
2 C2 5.5739 2.5835 36.0476 C.3 1 <0>1 0.1342
3 C3 5.4423 3.9542 36.7145 C.3 1 <0>1 -0.1375
4 C4 4.3803 2.3515 35.1187 C.3 1 <0>1 -0.1902
5 O1 6.8035 2.5359 35.2765 O.3 1 <0>1 -0.3277
6 C5 7.1636 3.6608 34.6304 C.2 1 <0>1 0.6728
7 O2 7.5982 4.6079 35.2555 O.2 1 <0>1 -0.5889
8 N1 7.0420 3.7367 33.2904 N.am 1 <0>1 -0.5349
9 N2 7.9261 4.4843 32.5655 N.3 1 <0>1 -0.2646
10 C6 8.1064 3.9270 31.2185 C.3 1 <0>1 0.0573
11 C7 7.7528 2.4620 31.2295 C.ar 1 <0>1 -0.0619
12 C8 8.1836 1.6548 32.2659 C.ar 1 <0>1 -0.0856
13 C9 7.8547 0.3122 32.2788 C.ar 1 <0>1 -0.1258
14 C10 7.1045 -0.2256 31.2497 C.ar 1 <0>1 -0.1252
15 C11 6.6790 0.5804 30.2106 C.ar 1 <0>1 -0.1230
16 C12 7.0029 1.9241 30.2005 C.ar 1 <0>1 -0.1032
17 C13 7.4995 5.8886 32.5014 C.3 1 <0>1 0.0294
18 H1 6.4117 5.9405 32.5520 H 1 <0>1 0.0993
19 C14 7.9789 6.5078 31.1871 C.3 1 <0>1 -0.0520
20 C15 9.0200 7.5582 31.4769 C.ar 1 <0>1 -0.0916
21 C16 8.7272 8.6016 32.3354 C.ar 1 <0>1 -0.0470
22 C17 9.6817 9.5628 32.6071 C.ar 1 <0>1 -0.2049
23 C18 10.9310 9.4864 32.0088 C.ar 1 <0>1 0.1124
24 C19 11.2204 8.4414 31.1433 C.ar 1 <0>1 -0.1530
25 C20 10.2644 7.4799 30.8793 C.ar 1 <0>1 -0.0793
26 O3 11.8699 10.4334 32.2705 O.3 1 <0>1 -0.3133
27 C21 11.8023 11.0797 33.5431 C.3 1 <0>1 0.1028
28 C22 10.3839 11.0425 34.0508 C.ar 1 <0>1 -0.0908
29 C23 9.3329 11.2750 33.1835 C.ar 1 <0>1 -0.0953
30 C24 8.0317 11.2359 33.6482 C.ar 1 <0>1 -0.1240
31 C25 7.7818 10.9748 34.9824 C.ar 1 <0>1 -0.1137
32 C26 8.8329 10.7479 35.8510 C.ar 1 <0>1 -0.1244
33 C27 10.1340 10.7815 35.3852 C.ar 1 <0>1 -0.0964
34 C28 8.0930 6.6474 33.6602 C.2 1 <0>1 0.4450
35 O4 8.2040 7.8490 33.6020 O.co2 1 <0>1 -0.6356
36 H2 6.4132 1.6968 37.8225 H 1 <0>1 0.0626
37 H3 4.6537 1.4860 37.6570 H 1 <0>1 0.0586
38 H4 5.7638 0.5243 36.6513 H 1 <0>1 0.0798
39 H5 5.3303 4.7215 35.9484 H 1 <0>1 0.0613
40 H6 4.5677 3.9594 37.3648 H 1 <0>1 0.0706
41 H7 6.3356 4.1581 37.3050 H 1 <0>1 0.0661
42 H8 4.4740 1.3751 34.6436 H 1 <0>1 0.0945
43 H9 3.4573 2.3870 35.6975 H 1 <0>1 0.0611
44 H10 4.3593 3.1274 34.3534 H 1 <0>1 0.0554
45 H11 6.3266 3.2604 32.8406 H 1 <0>1 0.4210
46 H12 7.4570 4.4521 30.5180 H 1 <0>1 0.0793
47 H13 9.1453 4.0477 30.9113 H 1 <0>1 0.0838
48 H14 8.7734 2.0740 33.0675 H 1 <0>1 0.1176
49 H15 8.1871 -0.3174 33.0909 H 1 <0>1 0.1129
50 H16 6.8508 -1.2753 31.2578 H 1 <0>1 0.1118
51 H17 6.0927 0.1602 29.4064 H 1 <0>1 0.1132
52 H18 6.6701 2.5540 29.3886 H 1 <0>1 0.1172
53 H19 8.4119 5.7314 30.5563 H 1 <0>1 0.0870
54 H20 7.1346 6.9656 30.6718 H 1 <0>1 0.0639
55 H21 7.7530 8.6629 32.7975 H 1 <0>1 0.1215
56 H22 9.4540 10.3752 33.2812 H 1 <0>1 0.1184
57 H23 12.1925 8.3797 30.6766 H 1 <0>1 0.1223
58 H24 10.4893 6.6660 30.2058 H 1 <0>1 0.1267
59 H25 12.4541 10.5632 34.2478 H 1 <0>1 0.0676
60 H26 12.1250 12.1159 33.4421 H 1 <0>1 0.0697
61 H27 9.5284 11.4834 32.1420 H 1 <0>1 0.1247
62 H28 7.2104 11.4128 32.9697 H 1 <0>1 0.1239
63 H29 6.7653 10.9479 35.3465 H 1 <0>1 0.1221
64 H30 8.6377 10.5441 36.8934 H 1 <0>1 0.1235
65 H31 10.9553 10.6043 36.0639 H 1 <0>1 0.1239
66 O5 8.4986 5.9883 34.7568 O.co2 1 <0>1 -0.7493
@<TRIPOS>BOND
1 1 2 1
2 1 36 1
3 1 37 1
4 1 38 1
5 2 3 1
6 2 4 1
7 2 5 1
8 3 39 1
9 3 40 1
10 3 41 1
11 4 42 1
12 4 43 1
13 4 44 1
14 5 6 1
15 6 7 2
16 6 8 am
17 8 9 1
18 8 45 1
19 9 10 1
20 9 17 1
21 10 11 1
22 10 46 1
23 10 47 1
24 11 16 ar
25 11 12 ar
26 12 13 ar
27 12 48 1
28 13 14 ar
29 13 49 1
30 14 15 ar
31 14 50 1
32 15 16 ar
33 15 51 1
34 16 52 1
35 17 18 1
36 17 19 1
37 17 34 1
38 19 20 1
39 19 53 1
40 19 54 1
41 20 25 ar
42 20 21 ar
43 21 22 ar
44 21 55 1
45 22 23 ar
46 22 56 1
47 23 24 ar
48 23 26 1
49 24 25 ar
50 24 57 1
51 25 58 1
52 26 27 1
53 27 28 1
54 27 59 1
55 27 60 1
56 28 33 ar
57 28 29 ar
58 29 30 ar
59 29 61 1
60 30 31 ar
61 30 62 1
62 31 32 ar
63 31 63 1
64 32 33 ar
65 32 64 1
66 33 65 1
67 34 35 ar
68 34 66 ar
@<TRIPOS>SUBSTRUCTURE
1 <0>1 1 TEMP 0 **** **** 0 ROOT
More information about the Dock-fans
mailing list