rubicon_hints.html

Daylight Summer School 2001, June 5-7, Santa Fe, NM

Daylight Worksheet - Rubicon...WITH HINTS

Rubicon, "Rule-Based Invention of Conformations", generates 3D coordinates for a TDT file using a simple set of rules, or rules generated from a training set with autorules.

Generate 3D coordinates to the drugs.tdt dataset created in the PCModels exercise or use the drugs.tdt file.

List Rubicon options

rubicon -options

sun1% rubicon -options
    NOTE: ========================================================== (rubicon)
    NOTE: == RUBICON v4.41 ================ 1995 (c) DAYLIGHT CIS == (rubicon)
    NOTE: ========================================================== (rubicon)
    NOTE:                                                            (rubicon)
    NOTE: Rubicon program options as implemented in v4.41 are:       (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -HELP or -help                                           (rubicon)
    NOTE:      Show syntax and help instructions                     (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -OPTIONS or -options                                     (rubicon)
    NOTE:      Show options summary (this info)                      (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -SETTINGS or -settings                                   (rubicon)
    NOTE:      Show options settings in effect                       (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -RUBE_ACCEPT_GRMS                                  (rubicon)
    NOTE:      Acceptable RMS of gradient vector for convergence     (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -RUBE_ACCEPT_MXDV                                  (rubicon)
    NOTE:      Acceptable maximum distance violation, Angstroms      (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -RUBE_ACCEPT_MXVV                                  (rubicon)
    NOTE:      Acceptable maximum volume violation, cubic Angstroms  (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -RUBE_ACCURACY                                      (rubicon)
    NOTE:      Effective machine accuracy                            (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -[NO]RUBE_BUMP14                                         (rubicon)
    NOTE:      (Don't) apply VDW bumping to nonbonded 1-4 distances  (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -RUBE_DEBUG                                        (rubicon)
    NOTE:      QUIET ..... no output on standard error               (rubicon)
    NOTE:      TERSE ..... only show progress                        (rubicon)
    NOTE:      ERRORS .... also show error messages                  (rubicon)
    NOTE:      WARNINGS .. also show warning messages                (rubicon)
    NOTE:      NOTES ..... also show notes                           (rubicon)
    NOTE:      DEBUG ..... also show debugging output                (rubicon)
    NOTE:      VERBOSE ... also show all debugging output            (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -[NO]RUBE_FILTER_CHIRAL                                  (rubicon)
    NOTE:      (Don't) enforce chirality in conformation filter.     (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -RUBE_FILTER_SLOP                             (rubicon)
    NOTE:      Minimum distance between equivalent atoms to consider (rubicon)
    NOTE:      conformations non-identical, Angstroms (off if 0.0).  (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -RUBE_FILTER_SMARTS                    (rubicon)
    NOTE:      SMARTS used for conformation filter atom matching.    (rubicon)
    NOTE:      If "USMILES", unique SMILES is used as target.        (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -RUBE_HYDROGENS                           (rubicon)
    NOTE:      ALL ....... include all hydrogens                     (rubicon)
    NOTE:      SOME ...... include specified hydrogens               (rubicon)
    NOTE:      NONE ...... suppress all normal hydrogens             (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -RUBE_LIMITEVAL                                 (rubicon)
    NOTE:      Limit function evaluations allowed per minimization   (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -RUBE_NCONFS                                     (rubicon)
    NOTE:      Number of conformations generated for each molecule   (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -RUBE_OUTPUT_FORMAT                             (rubicon)
    NOTE:      TDT ....... Write output in TDT format                (rubicon)
    NOTE:      PDB ....... write output in PDB format                (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -RUBE_RULES                                   (rubicon)
    NOTE:      Name(s) of Rubicon rule file(s)                       (rubicon)
    NOTE:      Rubicon rule file names typically end .rules          (rubicon)
    NOTE:      Quote if multiple, e.g. -RUBE_RULES "a.rules b.rules" (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -RUBE_RUNID                                  (rubicon)
    NOTE:      Add $D3DG generation item with runid to TDT output.   (rubicon)
    NOTE:      If set to "NONE", $D3DG item will not be output.      (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -RUBE_SEED                                         (rubicon)
    NOTE:      Random number seed in range 0 to 900000000            (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -RUBE_TRIALS                                       (rubicon)
    NOTE:      Number of trials per conformation                     (rubicon)
    NOTE:                                                            (rubicon)
    NOTE:   -[NO]RUBE_WRITE_BOUNDS                                   (rubicon)
    NOTE:      Add smoothed distance bounds matrix and list of       (rubicon)
    NOTE:      volume bounds to output (TDT output only).            (rubicon)
    NOTE:                                                            (rubicon)
    NOTE: ========================================================== (rubicon)
    NOTE: == RUBICON v4.41 ================ 1995 (c) DAYLIGHT CIS == (rubicon)
    NOTE: ========================================================== (rubicon)
    NOTE: -options request, exiting (rubicon)

List current settings

rubicon -settings

sun1% rubicon -settings
    NOTE: ========================================================== (rubicon)
    NOTE: == RUBICON v4.41 ================ 1995 (c) DAYLIGHT CIS == (rubicon)
    NOTE: ========================================================== (rubicon)
    NOTE:                                                            (rubicon)
    NOTE: Current values of Rubicon-specific options are:            (rubicon)
    NOTE:                                                            (rubicon)
    NOTE: RUBE_ACCEPT_GRMS .. 0.01                                   (rubicon)
    NOTE: RUBE_ACCEPT_MXDV .. 0.5                                    (rubicon)
    NOTE: RUBE_ACCEPT_MXVV .. 0.5                                    (rubicon)
    NOTE: RUBE_ACCURACY ..... 1e-20                                  (rubicon)
    NOTE: RUBE_BUMP14 ....... TRUE                                   (rubicon)
    NOTE: RUBE_DEBUG ........ QUIET                                  (rubicon)
    NOTE: RUBE_FILTER_CHIRAL  TRUE                                   (rubicon)
    NOTE: RUBE_FILTER_SLOP .. 0                                      (rubicon)
    NOTE: RUBE_FILTER_SMARTS  USMILES                                (rubicon)
    NOTE: RUBE_HYDROGENS .... ALL                                    (rubicon)
    NOTE: RUBE_LIMITEVAL .... 1000                                   (rubicon)
    NOTE: RUBE_NCONFS ....... 1                                      (rubicon)
    NOTE: RUBE_OUTPUT_FORMAT  TDT                                    (rubicon)
    NOTE: RUBE_RULES ........ $DY_ROOT/data/rubicon.rules            (rubicon)
    NOTE: RUBE_RUNID ........ NONE                                   (rubicon)
    NOTE: RUBE_SEED ......... 281191802                              (rubicon)
    NOTE: RUBE_TRIALS ....... 1                                      (rubicon)
    NOTE: RUBE_WRITE_BOUNDS . FALSE                                  (rubicon)
    NOTE:                                                            (rubicon)
    NOTE: ========================================================== (rubicon)
    NOTE: == RUBICON v4.41 ================ 1995 (c) DAYLIGHT CIS == (rubicon)
    NOTE: ========================================================== (rubicon)
    NOTE: -settings request, exiting (rubicon)

Generate 3D coordinates with standard ruleset

rubicon < drugs.tdt > drugs.3d.tdt

sun1% smi2tdt drugs.smi drugs.tdt
sun1% rubicon drugs.3d.tdt
opening rule file $DY_ROOT/data/rubicon.rules
sun1% more drugs.3d.tdt

$SMI<O=C1CC2OCC=C3CN4CCC56C4CC3C2C6N1c7ccccc75>
PCN<Strychnine>
$D3D<0.0;1/1;-1.27,3.70,0.64,-0.62,2.80,...
|
$SMI<COC(=O)C1C2CCC(CC1OC(=O)c3ccccc3)N2C>
PCN<cocaine>
$D3D<0.0;1/1;2.48,2.37,1.38,1.15,2.19,1.28,...
|
...

Generate 3D coordinates using rules generated from a training set and autorules. Obtain the training set from a substructural search of the medchem00 database and thorlookup to obtain the $D3D data.

Open the medchem00 database in merlin and search for a substructure from the drugs.tdt dataset.
Save the search results in a tdt file
```
sun1% smi2tdt nichits.tab nichits.tdt
```

Use thorlookup to find the $D3D data % thorlookup medchem00@SERVER:thor:thor%cognition -SECURE_PASSWORDS FALSE -INPUT_FORMAT TDT \ nichits.tdt nichitsfull.tdt Enter server access password for SERVER:thor:thor >> Enter password for database medchem00@SERVER:thor:* >>

generate a rule set

autorules < hitlist.tdt > output.rules

sun1% autorules < nichitsfull.tdt > outputrules
Unsigned volume rules .... OFF
Extremal SMILES output ... OFF
   10 tdts:    12 PAIR    21 TRIP    37 QUAD    16 BRAN     2 RING    88 total
   20 tdts:    29 PAIR    61 TRIP   112 QUAD    42 BRAN     3 RING   247 total
   30 tdts:    54 PAIR   125 TRIP   222 QUAD    75 BRAN     8 RING   484 total
   40 tdts:    63 PAIR   154 TRIP   285 QUAD    97 BRAN    10 RING   609 total
   50 tdts:    67 PAIR   164 TRIP   307 QUAD   106 BRAN    10 RING   654 total
   60 tdts:    75 PAIR   197 TRIP   396 QUAD   130 BRAN    15 RING   813 total
   70 tdts:    86 PAIR   237 TRIP   483 QUAD   158 BRAN    19 RING   983 total
   80 tdts:    92 PAIR   268 TRIP   569 QUAD   182 BRAN    23 RING  1134 total
   90 tdts:   100 PAIR   299 TRIP   653 QUAD   205 BRAN    29 RING  1286 total
  100 tdts:   116 PAIR   337 TRIP   749 QUAD   227 BRAN    35 RING  1464 total
  110 tdts:   122 PAIR   361 TRIP   807 QUAD   245 BRAN    39 RING  1574 total

Generate 3D structures for drugs.tdt dataset using the new ruleset

sun1% rubicon -RUBE_RULES output.rules drugs3dupdated.tdt opening rule file output.rules sun1% more drugs3dupdated.tdt ... $SMI<CN1CCCC1c2cccnc2> PCN<nicotine> $D3D<0.0;1/1;0.76,0.10,1.91,1.34,-0.44,0.72,2.50,0.24,0.20,2.48,-0.04,... | ... $SMI<CN1CCCC1c2cccnc2> PCN<nicotine> $D3D<0.0;1/1;1.17,-0.02,2.18,1.19,0.20,0.77,2.50,0.19,0.15,2.43,-0.83,... | ...

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