Conformer clustering
[What is a conformer clustering ?]
Classifying conformers into several meaningful groups is called a conformer clustering.
For example, we can obtain clusters consists of conformers that have a similar conformation, respectively, by grouping conformers based on structure parameters. It is possible to estimate how many conformers close to the most stable structure or a conformation in the X-ray crystal structure exist in what energy range.
In order to perform the conformer clustering, it needs a criterion to relate the conformers. The criterion for estimating how similar conformers is to a target conformer is called a distance between conformations. CONFLEX can perform the conformer clustering using RMSD values of dihedral angles or atomic coordinates as the structure parameter. The conformer clustering using RMSD value of dihedral angles as the distance between conformations is shown below as an example.
[Clustering all conformers of n-pentane]
This section explains how to perform a conformer clustering for all conformers of n-pentane.
First, we carry out a conformation search of n-pentane.
n-pentane.mol
n-pentane
17 16 0 0 0 0 0 0 0 0999 V2000
-1.2316 -1.9901 -0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.0874 -1.2286 -0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-0.1902 0.2689 -0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
1.1288 1.0304 -0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
0.8512 2.5279 -0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0
-1.0288 -3.0844 -0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0
-1.8145 -1.7213 0.9093 H 0 0 0 0 0 0 0 0 0 0 0 0
-1.8151 -1.7211 -0.9088 H 0 0 0 0 0 0 0 0 0 0 0 0
0.6703 -1.4973 -0.9093 H 0 0 0 0 0 0 0 0 0 0 0 0
0.6709 -1.4976 0.9088 H 0 0 0 0 0 0 0 0 0 0 0 0
-0.7731 0.5377 0.9093 H 0 0 0 0 0 0 0 0 0 0 0 0
-0.7737 0.5379 -0.9088 H 0 0 0 0 0 0 0 0 0 0 0 0
1.7117 0.7617 -0.9093 H 0 0 0 0 0 0 0 0 0 0 0 0
1.7123 0.7614 0.9088 H 0 0 0 0 0 0 0 0 0 0 0 0
1.8151 3.0844 -0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0
0.2683 2.7967 0.9093 H 0 0 0 0 0 0 0 0 0 0 0 0
0.2677 2.7969 -0.9088 H 0 0 0 0 0 0 0 0 0 0 0 0
1 2 1 0
1 6 1 0
1 7 1 0
1 8 1 0
2 3 1 0
2 9 1 0
2 10 1 0
3 4 1 0
3 11 1 0
3 12 1 0
4 5 1 0
4 13 1 0
4 14 1 0
5 15 1 0
5 16 1 0
5 17 1 0
M END
[Execution by Interface]
Open the n-pentane.mol file by CONFLEX Interface.
Select [CONFLEX] in Calculation menu, and click in the calculation setting dialog displayed.
In [General Settings] dialog on the detail setting dialog, select [Conformation Search] in the pull-down menu of [Calculation Type:].
Next, edit the value of [Search Limit:] to 4.0 in [Conformation Search] dialog on the detail setting dialog.
When the calculation settings are complete, click of the detail setting dialog.
When click , a dialog with the keywords for the calculation settings will be displayed.
Add [CHECK=(TORSION,NOENERGY)] keyword to the dialog. This keyword means that RMSD of dihedral angles around bonds in a backbone, not energy, is employed for the distance between conformations.
When you complete the addition, click . The calculation will start.
[Execution by command line]
The calculation settings are defined by describing keywords in the n-pentane.ini file.
n-pentane.ini file
MMFF94S CONFLEX SEL=4.0 CHECK=(TORSION,NOENERGY)
Explanations of each keyword are below.
| Keyword | Explanation |
|---|---|
| MMFF94S | Use MMFF94s force field |
| CONFLEX | Execute a conformation search |
| SEL=4.0 | Search limit sets to 4.0 kcal/mol. |
| CHECK=(TORSION,NOENERGY) | RMSD of dihedral angles around bonds in a backbone, not energy, is employed for the distance between conformations. |
Store the two files of n-pentane.mol and n-pentane.ini in an one folder, and execute below command. The calculation will start.
C:\CONFLEX\bin\flex9a_win_x64.exe -par C:\CONFLEX\par n-pentaneenter
The above command is for Windows OS. For the other OS, please refer to [How to execute CONFLEX].
Calculation results
After the search finished, we can get 11 conformers. The dihedral angles of C-C-C-C of each conformer are below.
Table: Dihedral angles of C-C-C-C of each conformer
| No. | Steric E | Dihedral angle | |
|---|---|---|---|
| 1-2-3-4 | 2-3-4-5 | ||
| 1 | -5.2718 | -180.00 | 180.00 |
| 2 | -4.4419 | 175.69 | 65.65 |
| 3 | -4.4419 | -65.65 | -175.69 |
| 4 | -4.4419 | 65.65 | 175.69 |
| 5 | -4.4419 | -175.69 | -65.65 |
| 6 | -3.8487 | 60.27 | 60.27 |
| 7 | -3.8487 | -60.27 | -60.27 |
| 8 | -1.5718 | -64.48 | 95.34 |
| 9 | -1.5718 | 95.34 | -64.48 |
| 10 | -1.5718 | -95.34 | 64.48 |
| 11 | -1.5718 | 64.48 | -95.34 |
Next, we perform a conformer clustering of 11 conformers using the dihedral angle around C2-C3 bond as the distance between conformations.
[Execution by Interface]
With the n-pentane.mol file open in CONFLEX Interface, select [CONFLEX] in Calculation menu, and click in the calculation setting dialog displayed.
After that, click in the detail setting dialog.
Edit the contents of the dialog as shown below, and click . The calculation will start.
Explanations of each keyword are below.
| Keyword | Explanation |
|---|---|
| NOSEARCH | Do not perform a conformation search |
| CLUSTER | Perform a conformer clustering |
| CCLUS_DISTANCE=TORSION | Use dihedral angle as the distance between conformations |
| CCLUS_LIMIT=10.0 | Group conformers with the distance between conformations within 10.0. |
| CCLUS_NREF=1 | The number of bonds to use as a criterion for clustering. |
| CLUS_IREF=(2,3) | Serial number of atoms consisting bond to use as a criterion for clustering. |
[Execution by command line]
Edit the contents in the n-pentane.ini file as shown below.
n-pentane.ini file
MMFF94S CONFLEX SEL=4.0 CHECK=(TORSION,NOENERGY) NOSEARCH CLUSTER CCLUS_DISTANCE=TORSION CCLUS_LIMIT=10.0 CCLUS_NREF=1 CCLUS_IREF=(2,3)
Explanations of each keyword are below.
| Keyword | Explanation |
|---|---|
| NOSEARCH | Do not perform a conformation search |
| CLUSTER | Perform a conformer clustering |
| CCLUS_DISTANCE=TORSION | Use dihedral angle as the distance between conformations |
| CCLUS_LIMIT=10.0 | Group conformers with the distance between conformations within 10.0. |
| CCLUS_NREF=1 | The number of bonds to use as a criterion for clustering. |
| CLUS_IREF=(2,3) | Serial number of atoms consisting bond to use as a criterion for clustering. |
Store the three files of n-pentane.mol, n-pentane.ini, and n-pentane.fxf in an one folder, and execute below command. The calculation will start.
C:\CONFLEX\bin\flex9a_win_x64.exe -par C:\CONFLEX\par n-pentaneenter
The above command is for Windows OS. For the other OS, please refer to [How to execute CONFLEX].
Calculation results
After the calculation finished, results of the conformer clustering are outputted in the n-pentane.clu file. Fist part in this file shows the number of conformers and index of the dihedral angle using as the distance between conformations.
=-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-=
CONFLEX CONFORMATIONAL CLUSTERING FILE
=-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-==-=
==============================================================================
# CLUSTERING INFORMATION
==============================================================================
CLUSTERING METHOD: SINGLE LINKAGE
NUMBER OF CONFORMERS CLUSTERED = 11 CONFORMERS (TOTAL 11 CONFORMERS)
DISTANCE (SIMILARITY) INDEX: TORSIONAL DISTANCE
DISTANCE DEFINITIONS: 1 TORSIONS
1: 1- 2- 3- 4
==============================================================================
Next, each the distance between conformations is listed.
[SORTED NUMBER] corresponds to the order of energy, and [CID NUMBER] corresponds to the order found during the conformation search. By this list, we find that the distance between 4th and 9th conformations is 1.1717 based on C1-C2-C3-C4 dihedral angle.
==============================================================================
# DISTANCE MATRIX ELEMENTS
==============================================================================
NUMBER OF DISTANCE MATIRX ELEMENTS = 55
SORTED NUMBER CID NUMBER DISTANCE
------------------ ------------------ ----------------------------
I J I J RMSD MAXD DRMSD
4 9 3 9 1.1717 -1.1717 0.0000
3 8 2 6 1.1717 1.1717 0.0000
6 9 7 9 4.2046 4.2046 3.0329
7 8 8 6 4.2046 -4.2046 0.0000
1 2 1 5 4.3141 -4.3141 0.1095
Finally, the result of conformer clustering with CCLUS_LIMIT=10.0 is outputted. The numbers in this table are [CID NUMBER], and they are shown in order of energy.
==============================================================================
# RESULT - 1 IN CID NUMBER
# MIN= 1, MAX= 3, AVERAGE= 2.00, DISPERSION= 5.640
==============================================================================
DISTANCE THRESHOLD= 10.00
NCLUSTERS= 5
SIZE= 3
1 5 4
SIZE= 3
2 8 6
SIZE= 3
3 7 9
SIZE= 1
11
SIZE= 1
10
==============================================================================
Next, using the result of conformation search obtained above, we perform a conformer clustering of 11 conformers using two dihedral angles as the distance between conformations.
[Execution by Interface]
With the n-pentane.mol file open in CONFLEX Interface, select [CONFLEX] in Calculation menu, and click in the calculation setting dialog displayed.
After that, click in the detail setting dialog.
Edit the contents of the dialog as shown below, and click . The calculation will start.
Here, CCLUS_LIMIT=70.0 set, and group the conformers with the distance between conformations within 70.0.
[CCLUS_NREF=2] set, and add [CCLUS_IREF=(3,4)]. This means that the dihedral angle around C3-C4 bond adds to the criterion for clustering.
[Execution by command line]
Edit the contents in the n-pentane.ini file as shown below.
n-pentane.ini file
MMFF94S CONFLEX SEL=4.0 CHECK=(TORSION,NOENERGY) NOSEARCH CLUSTER CCLUS_DISTANCE=TORSION CCLUS_LIMIT=70.0 CCLUS_NREF=2 CCLUS_IREF=(2,3) CCLUS_IREF=(3,4)
Here, CCLUS_LIMIT=70.0 set, and group the conformers with the distance between conformations within 70.0.
[CCLUS_NREF=2] set, and add [CCLUS_IREF=(3,4)]. This means that the dihedral angle around C3-C4 bond adds to the criterion for clustering.
Store the three files of n-pentane.mol, n-pentane.ini, and n-pentane.fxf in an one folder, and execute below command. The calculation will start.
C:\CONFLEX\bin\flex9a_win_x64.exe -par C:\CONFLEX\par n-pentaneenter
The above command is for Windows OS. For the other OS, please refer to [How to execute CONFLEX].
Calculation results
Depending on the setting change, each the distance between conformations will change as follow.
==============================================================================
# CLUSTERING INFORMATION
==============================================================================
CLUSTERING METHOD: SINGLE LINKAGE
NUMBER OF CONFORMERS CLUSTERED = 11 CONFORMERS (TOTAL 11 CONFORMERS)
DISTANCE (SIMILARITY) INDEX: TORSIONAL DISTANCE
DISTANCE DEFINITIONS: 2 TORSIONS
1: 1- 2- 3- 4
2: 2- 3- 4- 5
==============================================================================
# DISTANCE MATRIX ELEMENTS
==============================================================================
NUMBER OF DISTANCE MATIRX ELEMENTS = 55
SORTED NUMBER CID NUMBER DISTANCE
------------------ ------------------ ----------------------------
I J I J RMSD MAXD DRMSD
9 11 9 11 30.8622 30.8622 0.0000
8 10 6 10 30.8622 -30.8622 0.0000
4 9 3 9 62.9213 88.9765 32.0591
3 8 2 6 62.9213 -88.9765 0.0000
2 10 5 10 62.9213 88.9765 0.0000
5 11 4 11 62.9213 -88.9765 0.0000
Since CCLUS_LIMIT=70.0 set, 5, 10, 2, and 6 and 3, 9, 4, and 11 in CID NUMBER belong to same group, respectively.
==============================================================================
# RESULT - 1 IN CID NUMBER
# MIN= 1, MAX= 4, AVERAGE= 2.00, DISPERSION= 6.840
==============================================================================
DISTANCE THRESHOLD= 70.00
NCLUSTERS= 5
SIZE= 1
1
SIZE= 4
5 10 2 6
SIZE= 4
3 9 4 11
SIZE= 1
7
SIZE= 1
8
==============================================================================
[Clustering all conformers of β-Glucose]
Clustering of all conformers for β-Glucose using dihedral angles of 6-members ring as the distance between conformations is performed.
Store three files of clus-BGLU.mol, clus-BGLU.ini, and clus-BGLU.fxf in an one folder.
These files are in Sample_Files folder in the folder installed CONFLEX (Sample_Files\CONFLEX\clustering\b-glucose).
[Execution by Interface]
Open the clus-BGLU.mol file by CONFLEX Interface.
Select [CONFLEX] in Calculation menu, and click in the calculation setting dialog displayed.
After that, click in the detail setting dialog. A dialog with the keywords for the calculation settings will be displayed.
Add keywords to the dialog as shown below, and click . The calculation will start.
[Execution by command line]
The calculation settings have already written in the clus-BGLU.ini file.
clus-BGLU.ini file
MMFF94S CONFLEX NOSEARCH CLUSTER CCLUS_DISTANCE=TORSION CCLUS_LIMIT=10.0 CCLUS_NREF=6 CCLUS_IREF=(1,2) CCLUS_IREF=(2,10) CCLUS_IREF=(10,11) CCLUS_IREF=(11,3) CCLUS_IREF=(3,4) CCLUS_IREF=(4,1)
Execute below command. The calculation will start.
C:\CONFLEX\bin\flex9a_win_x64.exe -par C:\CONFLEX\par clus-BGLUenter
The above command is for Windows OS. For the other OS, please refer to [How to execute CONFLEX].
Calculation results
The conformers are classified by 7 groups according to the conformation of 6-members ring.
==============================================================================
# RESULT - 1 IN CID NUMBER
# MIN= 1, MAX= 122, AVERAGE= 31.00, DISPERSION= 2499.816
==============================================================================
DISTANCE THRESHOLD= 10.00
NCLUSTERS= 7
SIZE= 122
22 3 1 28 21 4
12 13 2 59 14 127
40 35 64 131 20 68
57 33 74 58 82 88
135 75 54 106 56 34
92 5 55 65 97 139
67 144 90 102 116 133
39 101 72 132 111 83
79 94 134 161 45 46
103 86 151 100 167 80
118 108 121 145 73 155
149 173 126 95 140 49
113 87 66 51 107 62
98 52 125 61 142 124
156 141 112 168 53 123
89 117 166 122 160 60
105 154 93 148 170 78
150 115 96 176 153 171
157 143 165 162 169 164
175 158 163 177 172 182
178 180
SIZE= 33
76 31 29 99 137 104
119 109 26 114 17 188
9 23 38 192 6 77
146 37 91 110 210 48
44 174 43 15 69 42
181 203 47
SIZE= 31
50 16 30 130 138 85
71 84 147 159 129 41
152 136 179 120 36 186
70 25 128 195 81 185
184 201 63 191 8 194
193
SIZE= 4
32 24 10 7
SIZE= 26
205 214 190 197 208 207
218 189 202 212 187 198
183 199 216 211 209 220
217 204 215 196 213 206
200 219
SIZE= 3
27 19 11
SIZE= 1
18
==============================================================================
The most stable structures in each group are shown below.
