Automated docking (DOCKER)¶
Finding the right interaction pattern of various molecules can be a tedious task and is typically based on chemical intuition. DOCKER is an energy driven algorithm to automatically dock atoms and moleuclar structures to form encounter complexes and aggregates.
Note
Note that the DOCKER algorithm is not fully parallelized at the moment, yet limiting the size of treatable systems. Full parallelization will be added in a future ORCA version.
The DOCKER in combination with Grimmes' efficient GFNn-xTB methods (GFN1-xTB, GFN2-xTB, GFN0-xTB, GFN-FF) can easily be envoked via simple input:
!DOCKER(GFN2-XTB)
%DOCKER
GUEST "guest.xyz"
END
*XYZFILE 0 1 host.xyz
Detailed functionality of DOCKER can be controlled via the %DOCKER block, for more information see the ORCA manual.
Example 1: Dimerization of Uracil¶
As a simple example, we can use DOCKER to create structure candidates for the uracil dimer. The used sample input looks like:
! XTB PAL8
%DOCKER
GUEST "uracil.xyz"
END
*XYZFILE 0 1 uracil.xyz
This calculation will dock two uracil monomers at the GFN2-xTB level in the gas-phase. The output of this calculations looks like:
***************
* ORCA Docker *
***************
Reading guests from file uracil.xyz
Number of structures read from file 1
Charge and multiplicity of guest from input
Docking approach independent
Docking level normal
Optimizing host .... -24.614947 Eh
Optimizing guest .... -24.614947 Eh
Starting Docker
---------------
Guest structure .... structure number 1
Guest charge and multiplicity .... (0 , 1)
Final charge and multiplicity .... (0 , 1)
PES used for swarm intelligence .... CDP
Setting random seed .... done
Creating spatial grid
Grid Center (x,y,z) 0.010, -0.361, -0.010 Angs
Grid Max Dimension 12.50 Angs
Angular Grid Step 14.40 degrees
Cartesian Grid Step 0.50 Angs
Cartesian points per Dimension 25 points
Angular points per Dimension 25 points
Initializing workers
Population Density 2.00 worker/Ang^2
Population Size 253
Swarm intelligence search
Minimization Algorithm mutant particle swarm
Min, Max Iterations (8 , 24)
Iter Emin avDE stdDE Time
(Eh) (kcal/mol) (kcal/mol) (min)
-------------------------------------------------------
1 -3.257928 >100 *** 0.00
2 -4.587273 >100 *** 0.00
3 -4.587273 >100 *** 0.00
4 -4.587273 >100 *** 0.00
5 -4.587273 >100 *** 0.00
6 -4.587273 >100 *** 0.00
7 -4.784278 >100 *** 0.00
8 -4.784278 >100 *** 0.00
9 -4.896772 >100 *** 0.00
10 -4.896772 >100 *** 0.00
11 -4.896772 >100 *** 0.00
12 -4.896772 >100 *** 0.00
13 -4.896772 >100 *** 0.00
14 -4.896772 >100 *** 0.00
15 -4.896772 >100 *** 0.00
16 -4.896772 >100 *** 0.00
No new minimum found after 8 (SwarmMinIter) steps.
Total time for swarm intelligence 0.00 minutes
Running preoptimization
Maximum number of structures 256
Optimization level sloppy
Coordinate system Cartesian
Potential energy surface GFN-FF
Fixed host false
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
31 32 33 34 35 36 37 38 39 40 41 42 43 44 45
46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
61 62 63 64 65 66 67 68 69 70 71 72 73 74 75
76 77 78 79 80 81 82 83 84 85 86 87 88 89 90
91 92 93 94 95 96 97 98 99 100 101 102 103 104 105
106 107 108 109 110 111 112 113 114 115 116 117 118 119 120
121 122 123 124 125 126 127 128 129 130 131 132 133 134 135
136 137 138 139 140 141 142 143 144 145 146 147 148 149 150
151 152 153 154 155 156 157 158 159 160 161 162 163 164 165
166 167 168 169 170 171 172 173 174 175 176 177 178 179 180
181 182 183 184 185 186 187 188 189 190 191 192 193 194 195
196 197 198 199 200 201 202 203 204 205 206 207 208 209 210
211 212 213 214 215 216 217 218 219 220 221 222 223 224 225
226 227 228 229 230 231 232 233 234 235 236 237 238 239 240
241 242 243 244 245 246 247 248 249 250 251 252 253
Time for 253 geometry preoptimizations : 1.30 minutes
All preoptimized structures saved to: orca.docker.struc1.all.preoptimized.xyz
Running final optimization
Maximum number of structures 16
Minimum energy difference 10.00 kcal/mol
Average RMSD 2.32 Angs
Optimization level normal
Coordinate system auto
Potential energy surface same as input
Fixed host false
Add final bias potential false
Struc Eopt Interaction Energy Time
(Eh) (kcal/mol) (min)
------------------------------------------------
1 -49.259335 -18.474094 0.01
2 -49.252949 -14.466709 0.01
3 -49.252952 -14.468874 0.01
4 -49.254738 -15.589752 0.01
5 -49.254917 -15.701695 0.01
6 -49.250438 -12.891437 0.01
7 -49.245042 -9.505268 0.01
8 -49.244197 -8.975114 0.01
9 -49.248582 -11.726407 0.02
10 -49.248397 -11.610503 0.03
11 -49.250422 -12.880850 0.03
12 -49.259348 -18.482195 0.05
13 -49.252992 -14.493875 0.02
14 -49.241697 -7.405797 0.03
15 -49.244203 -8.978954 0.03
16 -49.244181 -8.965084 0.03
Time for 16 geometry optimizations: 0.34 minutes
All optimized structures saved to : orca.docker.struc1.all.optimized.xyz
-------------------------------------
LOWEST INTERACTION ENERGY: -18.482195 kcal/mol (structure 12)
-------------------------------------
Total time for docking: 1.64 minutes
The lowest energy structure was 1, with energy -49.259348.
Docked structures saved to orca.docker.xyz
****ORCA-DOCKER TERMINATED NORMALLY****
We see that DOCKER generated 16 candidate structures and identified structure 12 as the energetically lowest one
which is stored in orca.docker.xyz. All other structures after optimization can be found in orca.docker.struc1.allopt.xyz.
Fig. 1: Energetically lowest uracil dimer structures generated by DOCKER (duplicates removed) with relative energies in kcal/mol.
Structures Example 1¶
Uracil
12
N -0.2707028 0.7632994 1.0276159
H -0.5957915 1.3097757 1.8163465
C -0.3386212 1.3810817 -0.2276640
O -0.7270425 2.5346295 -0.3329857
N 0.3638189 -1.2896563 0.1949192
H 0.0796815 0.9143946 -2.3190044
C 0.3781329 -0.7736192 -1.0714063
H 0.6499130 -1.4675080 -1.8526542
C 0.0669084 0.5154897 -1.3194961
H 0.4818502 -2.2779688 0.3498201
C -0.0016589 -0.5616540 1.3117092
O -0.0864879 -1.0482643 2.4227999
Example 2: Docking of cyclooctanol to \(\beta\)-CD¶
In this example, we will dock cyclooctanol to \(\beta\)-cyclodextrin. For very large molecules, using GFN2-xTB may become too costly. Therefore, we will exemplarily use the GFN-FF force-field in this example. The employed input looks like:
! XTBFF
%DOCKER
GUEST "cyclooctanol.xyz"
END
*XYZFILE 0 1 cyclodextrin.xyz
DOCKER yields the host-guest complex with cyclooctanol being located in the center of the cyclodextrin as the energetically most favorable structure. Other interaction motifs
with the alcohol being located at the outer rim of the cyclodextrin are also included in the orca.docker.struc1.allopt.xyz file.
Structures Example 2¶
Cyclooctanol
25
C -0.630732270324 0.540222793603 1.600761414434
C -1.432371159469 0.384302216526 -0.908462854692
C 1.671939879560 0.611757364766 -0.383488862093
C 1.551063510269 -0.552164900142 0.625485448688
C -0.346477476064 -0.353247209406 -1.713695099990
C 1.045411187360 0.298908175121 -1.752711207143
C -1.632861731037 -0.010632183198 0.575203191529
C 0.671032349882 -0.242300057237 1.849176839651
O -1.681185499105 -1.442691736454 0.751432117782
H -2.389914109012 -1.787025754614 0.185107018296
H -2.612389568993 0.409188132726 0.855678146000
H 1.144022454617 -1.433333371366 0.119148972672
H 1.197707493752 1.509427283252 0.030890091794
H -0.273875953996 -1.377678481706 -1.331024077317
H -1.149974959929 0.598772588999 2.565183251253
H -0.408068891048 1.576204730682 1.316751264090
H 0.421705955622 -1.184910127026 2.347531382837
H -2.397293252906 0.197426701475 -1.400917694821
H -0.691153740113 -0.445480421749 -2.750924529479
H 1.253716468584 0.348058633354 2.569678229592
H 1.712922614019 -0.377640668532 -2.303755614568
H -1.282960754333 1.472215430141 -0.954991499672
H 2.544099431570 -0.844333451745 0.985769664918
H 2.723584454521 0.879434706570 -0.537218529100
H 0.992053566569 1.225519605958 -2.340607064660
\(\beta\)-cyclodextrin
147
C -4.768156171798 1.055174471214 0.258034264598
C -5.404850114264 1.008927566532 -1.141456596734
C -5.701190428586 -0.444101356553 -1.500230499929
C -6.566922945568 -1.095132901509 -0.429444412072
C -5.944023234260 -0.909251015627 0.961874923878
O -5.723964169934 0.476062234654 1.190451853191
O -4.520893809964 1.495163779082 -2.156645399046
C -4.781180905736 2.785495817758 -2.701659708858
C -4.543203871423 2.694075892578 -4.215557614729
C -3.048268225489 2.523562281817 -4.505432294779
C -2.230087502276 3.551813448387 -3.716578005833
C -2.551561939665 3.489720490885 -2.222581311833
O -3.970183112270 3.772408736447 -2.088185165969
O -0.848972448174 3.220229881563 -3.972823367252
C -0.001236389272 4.252226558610 -4.406596252093
C 0.953480063919 3.686915101775 -5.462648372618
C 1.895893231101 2.678328559883 -4.825584398224
C 2.584582025984 3.292442363130 -3.610610243467
C 1.526609026582 3.791826443334 -2.621742016042
O 0.757976222371 4.801830284254 -3.328933192582
O 3.409605715924 2.243002608721 -3.069704656552
C 4.746389478908 2.564762741477 -2.768795904040
C 5.633800571134 1.389101419939 -3.201888064843
C 5.371252224410 0.166533483837 -2.332566235151
C 5.483102357163 0.525703331709 -0.853546498191
C 4.528748012529 1.693242161953 -0.551414423438
O 4.936742216352 2.814573101106 -1.385557869816
O 5.134487817667 -0.660049995090 -0.132449801880
C 5.952539099900 -1.031425707446 0.972739342125
C 6.131861164318 -2.555161365862 0.904908926769
C 4.802834265041 -3.244913503190 1.224388280876
C 4.198888590255 -2.665644970437 2.507493746443
C 4.045312029032 -1.146922608325 2.407433464451
O 5.379466587217 -0.610254575144 2.197707095291
O 2.926922822507 -3.330309928538 2.662232421037
C 2.630614066727 -3.881534426611 3.920907223146
C 1.922547167522 -5.227229696810 3.707421634115
C 0.551817638463 -5.016989699782 3.077313634888
C -0.260694697751 -4.007511809678 3.882617549830
C 0.547907479789 -2.706101601676 4.010196667646
O 1.790366838513 -3.033364246600 4.693387531977
O -1.483830121378 -3.815303255694 3.163900076592
C -2.699240328740 -3.847465365950 3.904850349300
O -3.139021281548 -2.539100508899 4.225857386154
C -3.342939889016 -1.709857330277 3.049597486344
C -4.474962771158 -2.359636494283 2.252037024700
C -4.105225680377 -3.784509478111 1.828894172820
C -3.722943770703 -4.615912753874 3.056643749726
C -3.594154377510 -0.279783175830 3.552142962223
O -2.589818816694 0.642920709410 3.117530044015
O -3.236397762468 -5.912242398683 2.749749090131
O -5.212042601529 -4.397233960459 1.174118957866
O -4.752209880113 -1.653261576766 1.024102271225
O -0.184550696744 -6.244343275918 3.034831446110
O 2.663959772304 -6.099272502801 2.828050722313
C -0.112067000745 -1.564788975500 4.798952693676
O -0.210337828193 -0.357681537935 4.036867304899
O 5.024881064493 -4.643095422996 1.382102424732
O 6.693911888860 -2.929159911725 -0.342283720488
C 3.466751479823 -0.434295482702 3.639050836220
O 2.329967007163 0.377175167644 3.324885499243
O 6.319709114461 -0.869819169395 -2.610127765329
O 5.385640514138 1.004133738539 -4.573485145543
C 4.504476233469 2.200136754824 0.898687559110
O 3.187722254955 2.200260420892 1.457696214264
O 2.843223282204 2.284149776002 -5.822911591096
O 0.175552532942 3.105298227672 -6.513301615039
C 2.045082050159 4.430729003200 -1.323104337841
O 1.602228075858 3.730031019422 -0.157179893914
O -2.828995557128 2.690563243358 -5.900312531915
O -5.361450625896 1.680849636558 -4.779032660480
C -1.808966539678 4.489684938930 -1.324427633829
O -1.121808041149 3.853924846599 -0.239077114847
O -6.363062932305 -0.461043290926 -2.769609870138
O -6.703112476703 -2.487830136598 -0.783945322535
C -4.405296214070 2.446534033100 0.798324514728
O -3.036824005234 2.539767647551 1.207129840321
H 3.282501152588 -6.623909218484 3.359804141215
H 0.359424928163 -6.877011821849 2.535528733781
H 6.285133583584 -2.369784363194 -1.033697694396
H 4.159944176031 -5.032762720855 1.619510868186
H 6.002521048463 1.486428693729 -5.145449345243
H 6.231259710207 -1.083463969856 -3.554365563580
H 0.788936658496 2.578163223515 -7.053446392765
H 3.480027836996 1.681959070868 -5.386839981618
H -5.371711197912 0.926347937718 -4.156101861598
H -1.863174074103 2.642813978645 -6.050615131415
H -7.559959726253 -2.808110299869 -0.461672686413
H -6.559462720613 -1.392607814634 -2.967083790286
H -2.274321366049 -5.839797958636 2.584878018179
H -5.449368934143 -3.809702710273 0.429090106313
H 3.544535229553 -3.999963094651 4.515228014857
H 1.789435496147 -5.704650688585 4.686084074183
H 0.684231199152 -4.618953148417 2.061116063118
H -0.477334697318 -4.413151186556 4.880893070069
H 0.780290402417 -2.338204097570 3.004421399265
H 6.922099169647 -0.526333128082 0.908982542462
H 6.858743114297 -2.846678771786 1.672090333889
H 4.095892583914 -3.054803281312 0.401743920374
H 4.843960636187 -2.917231928777 3.360985179551
H 3.419404232095 -0.906236088796 1.540367590235
H 5.041055251106 3.492832524909 -3.273354732515
H 6.682707475842 1.685617035325 -3.081304207251
H 4.349752102781 -0.193625552349 -2.520990208976
H 6.516596724781 0.814582460618 -0.615593368930
H 3.511213703141 1.395402704469 -0.828449405358
H -0.580626904781 5.089842049911 -4.808574818070
H 1.548764530724 4.524212430570 -5.855902194422
H 1.313210430051 1.809166344325 -4.486677451142
H 3.221643628606 4.131434935990 -3.923499381229
H 0.865393985329 2.959655760072 -2.354212277638
H -5.815383070098 3.078710183869 -2.492099247336
H -4.867013043957 3.639165160245 -4.666897323435
H -2.733411744973 1.520642301791 -4.175131113253
H -2.439368794773 4.559483474931 -4.101317728275
H -2.349902692928 2.476756832706 -1.855119427994
H -6.635347699959 -1.224463131275 1.752736462948
H -7.550382137333 -0.609081575538 -0.432016396941
H -4.745497378323 -0.984004916786 -1.563167159056
H -6.335870851237 1.593233867389 -1.149400157337
H -3.860506681274 0.440773406235 0.249985210931
H -2.540473527584 -4.349942718201 4.864862396316
H -4.625940538336 -4.758336220626 3.662070147545
H -3.238012752047 -3.725511536294 1.152880872379
H -5.386954103015 -2.387565486897 2.865063760371
H -2.428692056632 -1.711378877744 2.444669062802
H 5.102012255112 1.556471784745 1.545395233591
H 4.930258611752 3.211773749331 0.909875095609
H 2.595372882778 2.777610263973 0.907162433212
H 3.119861407675 -1.157260918060 4.378838888133
H 4.264263574140 0.173756452190 4.085107666173
H 2.596901075653 1.067977919648 2.663997123316
H -1.134374441476 -1.825751068025 5.076314424002
H 0.474286885712 -1.400575657062 5.712088646951
H 0.698183953811 -0.048771583135 3.780687207965
H -4.538940799705 0.108244537351 3.168270888790
H -3.642530759023 -0.309796438195 4.648243716770
H -1.705084692274 0.338085853057 3.448205273924
H 3.136031402146 4.414157741588 -1.285555212577
H 1.706380582059 5.474367166652 -1.300384402703
H -4.536712886388 3.207695474762 0.028489883983
H -5.075393688482 2.668265734511 1.638860044508
H -2.854558229596 1.872770519756 1.920563322474
H -1.044208224952 5.023593958024 -1.890558437435
H -2.539646925263 5.215314427524 -0.945212213485
H -1.782933735592 3.374553313446 0.326428735765
H 0.608666636607 3.759812187837 -0.120510919470