Docking studies are generally designed for predicting the affinity to biomolecules; however, there are many reports of applying this computational technique to other host-guest systems, where the host is not necessarily a biomolecule.
For example, many scientists perform the docking studies to predict the affinity of organic molecules to cyclodextrins (CDs). CDs are used as auxiliary substances which often contribute to enhanced solubility of the drug moleucle due to the formation of an inclusion complex. In tis context, docking studies allow to quickly predict the structure of such a complex.
For many common CDs, including α-, β- and γ-CD, the docking procedure enables obtaining satisfactory results.
However, the autogrid command failed for TRIMEB (heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin), in which all hydroxyl groups are substituted with methyl groups. This results in no "HD" atoms in PDBQT file.
Hence, my question is whether the lack of polar hydrogens was a true reason for autogrid failing?
(Luckily, the docking procedure finished succesfully when I changed the scoring function from AD4 to vina, and hence abandoned calculating the affinity maps.)
File TRIMEB.pdbqt:
HETATM 1 C11 TMB 1 1.839 -0.309 -5.963 1.00 0.00 0.292 C
HETATM 2 C21 TMB 1 1.044 -1.356 -6.742 1.00 0.00 0.207 C
HETATM 3 O21 TMB 1 -0.050 -0.819 -7.480 1.00 0.00 -0.383 OA
HETATM 4 C71 TMB 1 0.325 -0.299 -8.676 1.00 0.00 0.202 C
HETATM 5 C31 TMB 1 0.465 -2.373 -5.756 1.00 0.00 0.186 C
HETATM 6 O31 TMB 1 -0.190 -3.409 -6.448 1.00 0.00 -0.385 OA
HETATM 7 C81 TMB 1 -1.565 -3.593 -6.098 1.00 0.00 0.202 C
HETATM 8 C41 TMB 1 1.572 -2.955 -4.867 1.00 0.00 0.187 C
HETATM 9 O41 TMB 1 0.876 -3.679 -3.873 1.00 0.00 -0.348 OA
HETATM 10 C51 TMB 1 2.488 -1.879 -4.320 1.00 0.00 0.180 C
HETATM 11 O51 TMB 1 2.903 -0.957 -5.319 1.00 0.00 -0.348 OA
HETATM 12 C61 TMB 1 3.728 -2.417 -3.668 1.00 0.00 0.201 C
HETATM 13 O61 TMB 1 4.321 -3.332 -4.533 1.00 0.00 -0.393 OA
HETATM 14 C91 TMB 1 5.505 -3.966 -3.940 1.00 0.00 0.201 C
HETATM 15 C12 TMB 1 1.443 -4.861 -3.388 1.00 0.00 0.292 C
HETATM 16 C22 TMB 1 0.355 -5.875 -3.162 1.00 0.00 0.207 C
HETATM 17 O22 TMB 1 -0.381 -6.162 -4.328 1.00 0.00 -0.383 OA
HETATM 18 C72 TMB 1 0.416 -6.669 -5.459 1.00 0.00 0.202 C
HETATM 19 C32 TMB 1 -0.628 -5.408 -2.138 1.00 0.00 0.186 C
HETATM 20 O32 TMB 1 -1.530 -6.475 -1.823 1.00 0.00 -0.385 OA
HETATM 21 C82 TMB 1 -2.819 -6.344 -2.477 1.00 0.00 0.202 C
HETATM 22 C42 TMB 1 0.074 -5.023 -0.813 1.00 0.00 0.187 C
HETATM 23 O42 TMB 1 -0.795 -4.364 0.012 1.00 0.00 -0.348 OA
HETATM 24 C52 TMB 1 1.277 -4.087 -1.195 1.00 0.00 0.180 C
HETATM 25 O52 TMB 1 2.094 -4.576 -2.130 1.00 0.00 -0.348 OA
HETATM 26 C62 TMB 1 1.751 -3.070 0.087 1.00 0.00 0.201 C
HETATM 27 O62 TMB 1 2.301 -3.954 0.879 1.00 0.00 -0.393 OA
HETATM 28 C92 TMB 1 3.111 -3.306 1.924 1.00 0.00 0.201 C
HETATM 29 C13 TMB 1 -1.474 -5.212 0.971 1.00 0.00 0.292 C
HETATM 30 C23 TMB 1 -2.642 -4.588 1.493 1.00 0.00 0.207 C
HETATM 31 O23 TMB 1 -3.510 -4.155 0.413 1.00 0.00 -0.383 OA
HETATM 32 C73 TMB 1 -4.787 -4.677 0.338 1.00 0.00 0.202 C
HETATM 33 C33 TMB 1 -2.383 -3.328 2.387 1.00 0.00 0.186 C
HETATM 34 O33 TMB 1 -3.639 -2.996 2.956 1.00 0.00 -0.385 OA
HETATM 35 C83 TMB 1 -3.846 -1.655 2.913 1.00 0.00 0.202 C
HETATM 36 C43 TMB 1 -1.339 -3.660 3.403 1.00 0.00 0.187 C
HETATM 37 O43 TMB 1 -0.975 -2.423 4.006 1.00 0.00 -0.348 OA
HETATM 38 C53 TMB 1 -0.121 -4.288 2.800 1.00 0.00 0.180 C
HETATM 39 O53 TMB 1 -0.616 -5.495 2.051 1.00 0.00 -0.348 OA
HETATM 40 C63 TMB 1 1.000 -4.820 3.699 1.00 0.00 0.201 C
HETATM 41 O63 TMB 1 0.495 -5.461 4.842 1.00 0.00 -0.393 OA
HETATM 42 C93 TMB 1 0.087 -6.830 4.607 1.00 0.00 0.201 C
HETATM 43 C14 TMB 1 -0.221 -2.447 5.299 1.00 0.00 0.292 C
HETATM 44 C24 TMB 1 -1.166 -1.810 6.337 1.00 0.00 0.207 C
HETATM 45 O24 TMB 1 -2.429 -2.458 6.458 1.00 0.00 -0.383 OA
HETATM 46 C74 TMB 1 -2.331 -3.735 7.042 1.00 0.00 0.202 C
HETATM 47 C34 TMB 1 -1.387 -0.370 6.040 1.00 0.00 0.186 C
HETATM 48 O34 TMB 1 -1.992 0.271 7.158 1.00 0.00 -0.385 OA
HETATM 49 C84 TMB 1 -3.358 0.511 6.999 1.00 0.00 0.202 C
HETATM 50 C44 TMB 1 -0.126 0.379 5.744 1.00 0.00 0.187 C
HETATM 51 O44 TMB 1 -0.501 1.638 5.141 1.00 0.00 -0.348 OA
HETATM 52 C54 TMB 1 0.762 -0.352 4.750 1.00 0.00 0.180 C
HETATM 53 O54 TMB 1 0.943 -1.748 5.189 1.00 0.00 -0.348 OA
HETATM 54 C64 TMB 1 2.180 0.218 4.777 1.00 0.00 0.201 C
HETATM 55 O64 TMB 1 2.866 -0.209 3.616 1.00 0.00 -0.393 OA
HETATM 56 C94 TMB 1 4.278 0.290 3.621 1.00 0.00 0.201 C
HETATM 57 C15 TMB 1 -0.024 2.834 5.687 1.00 0.00 0.292 C
HETATM 58 C25 TMB 1 -1.073 3.891 5.633 1.00 0.00 0.207 C
HETATM 59 O25 TMB 1 -2.221 3.539 6.342 1.00 0.00 -0.383 OA
HETATM 60 C75 TMB 1 -2.055 3.590 7.775 1.00 0.00 0.202 C
HETATM 61 C35 TMB 1 -1.471 4.184 4.227 1.00 0.00 0.186 C
HETATM 62 O35 TMB 1 -2.272 5.369 4.120 1.00 0.00 -0.385 OA
HETATM 63 C85 TMB 1 -3.604 5.154 4.219 1.00 0.00 0.202 C
HETATM 64 C45 TMB 1 -0.257 4.448 3.379 1.00 0.00 0.187 C
HETATM 65 O45 TMB 1 -0.640 4.370 1.967 1.00 0.00 -0.348 OA
HETATM 66 C55 TMB 1 0.892 3.477 3.584 1.00 0.00 0.180 C
HETATM 67 O55 TMB 1 1.126 3.277 5.000 1.00 0.00 -0.348 OA
HETATM 68 C65 TMB 1 2.159 4.047 2.999 1.00 0.00 0.201 C
HETATM 69 O65 TMB 1 2.466 5.285 3.656 1.00 0.00 -0.393 OA
HETATM 70 C95 TMB 1 3.619 5.944 3.080 1.00 0.00 0.201 C
HETATM 71 C16 TMB 1 -0.685 5.608 1.270 1.00 0.00 0.292 C
HETATM 72 C26 TMB 1 -1.863 5.605 0.321 1.00 0.00 0.207 C
HETATM 73 O26 TMB 1 -3.053 5.219 1.014 1.00 0.00 -0.383 OA
HETATM 74 C76 TMB 1 -4.009 6.245 1.024 1.00 0.00 0.202 C
HETATM 75 C36 TMB 1 -1.680 4.640 -0.826 1.00 0.00 0.186 C
HETATM 76 O36 TMB 1 -2.743 4.939 -1.793 1.00 0.00 -0.385 OA
HETATM 77 C86 TMB 1 -3.572 3.798 -2.030 1.00 0.00 0.202 C
HETATM 78 C46 TMB 1 -0.380 4.921 -1.513 1.00 0.00 0.187 C
HETATM 79 O46 TMB 1 -0.191 3.888 -2.480 1.00 0.00 -0.348 OA
HETATM 80 C56 TMB 1 0.769 4.824 -0.471 1.00 0.00 0.180 C
HETATM 81 O56 TMB 1 0.512 5.801 0.534 1.00 0.00 -0.348 OA
HETATM 82 C66 TMB 1 2.141 5.082 -1.012 1.00 0.00 0.201 C
HETATM 83 O66 TMB 1 2.279 6.302 -1.637 1.00 0.00 -0.393 OA
HETATM 84 C96 TMB 1 3.320 7.100 -1.201 1.00 0.00 0.201 C
HETATM 85 C17 TMB 1 0.382 4.274 -3.749 1.00 0.00 0.292 C
HETATM 86 C27 TMB 1 -0.528 3.772 -4.888 1.00 0.00 0.207 C
HETATM 87 O27 TMB 1 -1.904 4.097 -4.729 1.00 0.00 -0.383 OA
HETATM 88 C77 TMB 1 -2.153 5.501 -4.940 1.00 0.00 0.202 C
HETATM 89 C37 TMB 1 -0.518 2.239 -4.964 1.00 0.00 0.186 C
HETATM 90 O37 TMB 1 -1.193 1.832 -6.136 1.00 0.00 -0.385 OA
HETATM 91 C87 TMB 1 -2.184 0.862 -5.899 1.00 0.00 0.202 C
HETATM 92 C47 TMB 1 0.959 1.803 -5.055 1.00 0.00 0.187 C
HETATM 93 O47 TMB 1 0.950 0.357 -5.037 1.00 0.00 -0.348 OA
HETATM 94 C57 TMB 1 1.736 2.317 -3.884 1.00 0.00 0.180 C
HETATM 95 O57 TMB 1 1.668 3.794 -3.929 1.00 0.00 -0.348 OA
HETATM 96 C67 TMB 1 3.176 1.950 -3.776 1.00 0.00 0.201 C
HETATM 97 O67 TMB 1 3.719 2.220 -4.964 1.00 0.00 -0.393 OA
HETATM 98 C97 TMB 1 5.107 1.720 -5.085 1.00 0.00 0.201 C
TER 99 TMB 1
File TRIMEB.gpf:
npts 40 40 40 # num.grid points in xyz
gridfld TRIMEB.maps.fld # grid_data_file
spacing 0.375 # spacing(A)
receptor_types C OA # receptor atom types
ligand_types A C HD OA # ligand atom types
receptor TRIMEB.pdbqt # macromolecule
gridcenter 0.302 0.078 -0.062 # xyz-coordinates or auto
smooth 0.5 # store minimum energy w/in rad(A)
map TRIMEB.A.map # atom-specific affinity map
map TRIMEB.C.map # atom-specific affinity map
map TRIMEB.HD.map # atom-specific affinity map
map TRIMEB.OA.map # atom-specific affinity map
elecmap TRIMEB.e.map # electrostatic potential map
dsolvmap TRIMEB.d.map # desolvation potential map
dielectric -0.1465 # <0, AD4 distance-dep.diel;>0, constant
File TRIMEB.glg:
$Revision: 1.160 $
Compilation parameters: NUM_RECEPTOR_TYPES=20 NEINT=1024
AG_MAX_ATOMS=100000 AG_MAX_NBONDS=4 MAX_MAPS=128 NDIEL=8192 MAX_ATOM_TYPES=126
e_vdW_Hb table allows 15876 entries of size 1024
Maximum number of maps that can be computed = 128 (defined by MAX_MAPS in "autocomm.h").
Non-bond cutoff for internal energy calculation (SOFTNBC): 8.00
Optimize internal energy scoring (USE_8A_NBCUTOFF): yes
Faster search for nearby atoms (USE_BHTREE): no
Run calculations in parallel if possible (_OPENMP): yes
Maximum number of parallel threads (MAXTHREADS): 32
This file was created at: 1:56 21" p.m., 05/21/2026
using: "unknown_host"
GPF> npts 40 40 40 # num.grid points in xyz
Number of grid points in x-direction: 41
Number of grid points in y-direction: 41
Number of grid points in z-direction: 41
GPF> gridfld TRIMEB.maps.fld # grid_data_file
Creating (AVS-readable) grid maps file : TRIMEB.maps.fld
Creating (AVS-readable) grid-coordinates extrema file : TRIMEB.maps.xyz
GPF> spacing 0.375 # spacing(A)
Grid Spacing : 0.375 Angstrom
GPF> receptor_types C OA # receptor atom types
GPF> ligand_types A C HD OA # ligand atom types
0 'A' ->'A' vdW/Hb/cov
1 'C' ->'C' vdW/Hb/cov
2 'HD' ->'HD' vdW/Hb/cov
3 'OA' ->'OA' vdW/Hb/cov
Allocated space for 6 gridmap objects
8 CPU threads will be used for calculation
Atom type names for ligand atom types 1-4 used for ligand-atom affinity grid maps:
Atom type number 1 corresponds to atom type name "A".
Atom type number 2 corresponds to atom type name "C".
Atom type number 3 corresponds to atom type name "HD".
Atom type number 4 corresponds to atom type name "OA".
GPF> receptor TRIMEB.pdbqt # macromolecule
Receptor Input File : TRIMEB.pdbqt
Receptor Atom Type Assignments:
Maximum partial atomic charge found = +0.292 e
Minimum partial atomic charge found = -0.393 e
Atom Atom Number of this Type
Type ID in Receptor
____ ____ ___________________
0 C 63
1 OA 35
Total number of atoms : 98 atoms
Total charge : 0.01 e
Receptor coordinates fit within the following volume:
_______(5.5, 7.1, 7.8)
/| /|
/ | / |
/______/ |
| |___|__| Midpoint = (0.4, 0.1, -0.5)
| / | /
| / | /
|/_____|/
(-4.8, -6.8, -8.7)
Maximum coordinates : (5.505, 7.100, 7.775)
Minimum coordinates : (-4.787, -6.830, -8.676)
GPF> gridcenter 0.302 0.078 -0.062 # xyz-coordinates or auto
Grid maps will be centered on user-defined coordinates:
(0.302, 0.078, -0.062)
Grid maps will cover the following volume:
_______(7.8, 7.6, 7.4)
/| /|
/ | / |
/______/ |
| |___|__| Midpoint = (0.3, 0.1, -0.1)
| / | /
| / | /
|/_____|/
(-7.2, -7.4, -7.6)
Grid map x-dimension : 15.0 Angstroms
Grid map y-dimension : 15.0 Angstroms
Grid map z-dimension : 15.0 Angstroms
Maximum coordinates : (7.802, 7.578, 7.438)
Minimum coordinates : (-7.198, -7.422, -7.562)
GPF> smooth 0.5 # store minimum energy w/in rad(A)
Potentials will be smoothed by: 0.500 Angstrom
GPF> map TRIMEB.A.map # atom-specific affinity map
Output Grid Map 1: TRIMEB.A.map
GPF> map TRIMEB.C.map # atom-specific affinity map
Output Grid Map 2: TRIMEB.C.map
GPF> map TRIMEB.HD.map # atom-specific affinity map
Output Grid Map 3: TRIMEB.HD.map
GPF> map TRIMEB.OA.map # atom-specific affinity map
Output Grid Map 4: TRIMEB.OA.map
GPF> elecmap TRIMEB.e.map # electrostatic potential map
Output Electrostatic Potential Energy Grid Map: TRIMEB.e.map
GPF> dsolvmap TRIMEB.d.map # desolvation potential map
Output Desolvation Free Energy Grid Map: TRIMEB.d.map
GPF> dielectric -0.1465 # <0, AD4 distance-dep.diel;>0, constant
Using *distance-dependent* dielectric function of Mehler and Solmajer, Prot.Eng.4, 903-910.
>>> Closing the grid parameter file (GPF)... <<<
________________________________________________________________________________
No Floating Grid was requested.
No Constriction Grid was requested.
Calculating Pairwise Interaction Energies
Beginning grid calculations.
Calculating 6 grids over 68921 elements, around 98 receptor atoms.
Percent Estimated Time Time/this plane
XY-plane Z-coord Done Remaining Real, User, System
/Ang /sec /sec
________ ________ ________ ______________ __________________________
autogrid4: ERROR: no closestH atom was found
autogrid4: Unsuccessful Completion.
The .map files contain only headers:
GRID_PARAMETER_FILE TRIMEB.gpf
GRID_DATA_FILE TRIMEB.maps.fld
MACROMOLECULE TRIMEB.pdbqt
SPACING 0.375
NELEMENTS 40 40 40
CENTER 0.302 0.078 -0.062
Docking studies are generally designed for predicting the affinity to biomolecules; however, there are many reports of applying this computational technique to other host-guest systems, where the host is not necessarily a biomolecule.
For example, many scientists perform the docking studies to predict the affinity of organic molecules to cyclodextrins (CDs). CDs are used as auxiliary substances which often contribute to enhanced solubility of the drug moleucle due to the formation of an inclusion complex. In tis context, docking studies allow to quickly predict the structure of such a complex.
For many common CDs, including α-, β- and γ-CD, the docking procedure enables obtaining satisfactory results.
However, the
autogridcommand failed for TRIMEB (heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin), in which all hydroxyl groups are substituted with methyl groups. This results in no "HD" atoms in PDBQT file.Hence, my question is whether the lack of polar hydrogens was a true reason for
autogridfailing?(Luckily, the docking procedure finished succesfully when I changed the scoring function from
AD4tovina, and hence abandoned calculating the affinity maps.)File
TRIMEB.pdbqt:File
TRIMEB.gpf:File
TRIMEB.glg:The
.mapfiles contain only headers: