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 PAL4
%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 during evolution .... GFN2-XTB
Setting random seed .... done
Creating spatial grid
Grid Max Dimension 12.50 Angs
Angular Grid Step 14.40 degrees
Cartesian Grid Step 0.50 Angs
Points per Dimension 25 points
Initializing workers
Population Density 0.50 worker/Ang^2
Population Size 123
Evolving structures
Minimization Algorithm mutant particle swarm
Min, Max Iterations (3 , 10)
Iter Emin avDE stdDE Time
(Eh) (Eh) (ang) (min)
-------------------------------------------------------
1 -49.254341 9.888241 3.233712 0.62
2 -49.258510 10.477635 3.390259 0.65
3 -49.258510 9.521873 2.969795 0.65
4 -49.258510 8.793785 2.942822 0.65
No new minimum found after 3 (MinIter) steps.
Total time for evolution 2.57 minutes
Running final optimization
Maximum number of structures 11
Minimum energy difference 0.10 kcal/mol
Maximum RMSD 0.25 Angs
Optimization strategy regular
Coordinate system redundant 2022
Fixed host false
Struc Eopt Interaction Energy Time
(Eh) (kcal/mol) (min)
------------------------------------------------
1 -49.248577 -11.723427 0.07
2 -49.250442 -12.893751 0.07
3 -49.245624 -9.870339 0.04
4 -49.252991 -14.493130 0.06
5 -49.248470 -11.656256 0.05
6 -49.259335 -18.474228 0.05
7 -49.259264 -18.429538 0.08
8 -49.254913 -15.699019 0.04
9 -49.254927 -15.708244 0.04
10 -49.241672 -7.390198 0.03
11 -49.246534 -10.441269 0.04
Time for 11 geometry optimizations: 0.58 minutes
All optimized structures saved to : orca.docker.struc1.allopt.xyz
-------------------------------------
LOWEST INTERACTION ENERGY: -18.474228 kcal/mol (structure 6)
-------------------------------------
Total time for docking: 3.19 minutes
The lowest energy structure was 1, with energy -49.259335.
Docked structures saved to orca.docker.xyz
****ORCA-DOCKER TERMINATED NORMALLY****
We see that DOCKER generated 11 candidate structures and identified structure 6 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: 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: Generation of (MeCp)Mn(CO)3#
In our second example, we will automatically generate (MeCp)Mn(CO)3, also known as MCMT, a prominent antiknock reagent. To do so, we will start from a Mn+ ion and use DOCKER to coordinate MeCp- and three CO ligands. For the initial coordination of MeCp-, the input file looks like the following:
! XTB
%DOCKER
GUEST "mecp.xyz"
GuestCharge -1
END
*XYZ 1 1
Mn 0 0 0
*
In this case, we assume that Mn+ has a closed-shell 3d6 configuration and the charge of the MeCp- is set to -1. After the successful coordination of MeCp-,
we want to add three CO ligands to the (MeCp)Mn complex. To do so, we use the NRepeatGuest option in the %DOCKER block.
! XTB
%DOCKER
GUEST "co.xyz"
NRepeatGuest 3
END
*XYZFILE 0 1 mecpmn.xyz
DOCKER now successively adds three CO ligands. The lowest energy structures obtained from the docking tasks are visualized in the following:
Structures Example 2#
MeCp-
13
C -3.64427622132568 3.09316683643494 0.01091629612016
C -3.87999219107613 2.51600304373552 1.25660734396560
C -2.65274176334490 2.12553705874125 1.78901754813097
C -1.65193000677097 2.45920643455840 0.87321354895126
C -2.27129809643429 3.05878854146220 -0.22576830966736
H -4.39748886822314 3.49586021999700 -0.66020373614263
H -4.84980591903549 2.38868239855723 1.72914527345892
H -2.49667408630002 1.64042064054602 2.74824348877019
H 0.32165777036830 2.14198139178304 0.08049985624744
H -1.76541215415890 3.42885463317223 -1.11296797433561
H 0.30624914501611 3.06684333388484 1.58428181364891
C -0.17765723116959 2.23720831134323 1.04896114415727
H 0.01898370151214 1.32580055067847 1.62184463601315
CO
2
C 0.17457487970377 0.17457487970377 0.17457487970377
O 0.82542512029623 0.82542512029623 0.82542512029623
(MeCp)Mn(CO)3
20
Mn 0.10772025158918877019 0.81212587335336905436 -1.92171687668995194720
C 0.43167555634988569180 2.93675983488815095512 -1.83871863568744564610
C -0.63752834317906326156 2.66571247544714085009 -2.71909965291139421595
C -0.13396552236281986104 1.87780830368776330275 -3.78868516508951946875
C 1.25981510310186650692 1.69221580813308847269 -3.59264603016447070516
C 1.59750708039633160240 2.31699309621178395346 -2.36361211321316444511
H 0.40657825604932584795 3.62569053823126674629 -1.00455233931485121701
H -1.62297332911990621618 3.11079681509173155973 -2.67506328708324714327
H -0.66985357831151026708 1.64130628469667350089 -4.69871163430750549139
H 2.55690064213908341273 1.95515857280974292287 -5.25054887769718092727
H 2.60580860691424787134 2.47173017653485782574 -2.00214023348514480460
H 3.10260418224006251364 0.71975088588299618308 -4.11234615985394214022
C 2.22543258111944686206 1.14467797515485525395 -4.59710627144102712549
H 1.76131130861969520396 0.37866263578440867432 -5.21584341734327683326
C 0.83920336042927801135 -0.76204682118684241576 -2.33671046519168701394
O 1.34461847467276229828 -1.74307886048269322643 -2.65547492857369826780
C 0.43423449309114875438 0.64416016169359235910 -0.17566096895699659375
O 0.66488528228962273658 0.59271701978585245030 0.94801502974767526410
C -1.54261490113692767423 0.14793316793256136576 -1.78391727528337851183
O -2.62372995624129723424 -0.23489302928064861864 -1.72713471935651186051
Example 3: 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 3#
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