Daylight Worksheet - PCModels/PCFilters --WITH HINTS!

PCModels can be used from an XView interface (xvpcmodels) or from the command line (clogp and cmr). These exercises will introduce you to xvpcmodels and teach you how to generate and interpret clogp/cmr values for a test dataset.

1. Calculate clogp and cmr value for dopamine (NCCc1ccc(O)c(O)c1) and compare with results from the last exercise using xvpcmodels.

   xvpcmodels
   

   • Type in SMILES for dopamine or draw in the structure using Grins

   • Select options for Model, Output and Depict

   • Select Compute

   • Try out various Output options

2. Calculate clogp and cmr values for the SAMPLE.medchem.smi dataset. (file is at http://www.daylight.com/meetings/summerschool00/files/data/SAMPLE.medchem.smi)

With right mouse button in white background of the input window select "File-->Open" and the following window will appear

The contents of the SAMPLE.medchem.smi data set should appear in the Input window

• Get options for clogp and cmr

  clogp +HELP

  sun1% clogp +HELP
  +----------------------------------------------------------+
  | CLOGP -- Add CLOGP results from/to .TDT files            |
  +----------------------------------------------------------+
  | Copyright (c) 1990-1997 Daylight CIS, Inc.               |
  | Copyright (c) 1985-1997 Pomona College                   |
  +----------------------------------------------------------+
  | $ clogp [options] [infile.tdt [outfile.tdt]]             |
  |     Copy .TDT input file to output file, adding CLOGP    |
  |     polarizability estimate as a CLOGP datum.  The CLOGP |
  |     datatype has 3 fields:  CP.   |
  |     Output to standard output if second argument is      |
  |     missing. Input from standard input if no arguments   |
  |     are given.  Exit w/ warning if CLOGP is inaccessible;|
  |     copy unchanged input tree to output on other errors, |
  |     e.g., invalid input, CLOGP can't make valid estimate.|
  |                                                          |
  | $ clogp +HELP                                            |
  |     Write this help message to standard output and exit. |
  |                                                          |
  | $ clogp +PCMODELS_VERSION                                |
  |     Write the version number of the CLOGP program to     |
  |     standard output (e.g. 4.61) and exit.  If CLOGP      |
  |     program is not accessible for any reason, write 000. |
  |     NOTE: This returns the Daylight program version.     |
  |           It is different than the algorithm or database |
  |           versions, which are from Biobyte and are       |
  |           algorithm 3.05 and database version 17.        |
  |           The Biobyte version numbers appear in the      |
  |           table output of ClogP.                         |
  |                                                          |
  | $ clogp +PCMODELS_ERRORTEXT                              |
  |     Write a list of English translations of all possible |
  |     CLOGP error levels to standard output and exit.      |
  |     Format is: $I<-{errorlevel}P;{translation}>|.        |
  |                                                          |
  | $ clogp +PCMODELS_TABLEOUTPUT                            |
  |     Set output format to verbose tables.                 |
  |                                                          |
  | $ clogp +PCMODELS_DUMPFRAGDB                             |
  |     Dump fragment database to standard output and exit.  |
  +----------------------------------------------------------+
  
  

  cmr +HELP

  sun1% cmr +HELP
  +----------------------------------------------------------+
  | CMR -- Add CMR results from/to .TDT files                |
  +----------------------------------------------------------+
  | Copyright (c) 1990-1997 Daylight CIS, Inc.               |
  | Copyright (c) 1985-1997 Pomona College                   |
  +----------------------------------------------------------+
  | $ cmr [options] [infile.tdt [outfile.tdt]]               |
  |     Copy .TDT input file to output file, adding CMR      |
  |     molar refractivity estimate as a CMR datum.  The CMR |
  |     datatype has 3 fields:  CR.   |
  |     Output to standard output if second argument is      |
  |     missing.  Input from standard input if no arguments  |
  |     are given.  Exit with warning if CMR is inaccessible;|
  |     copy unchanged input tree to output on other errors, |
  |     e.g., invalid input, CMR can't make valid estimate.  |
  |                                                          |
  | $ cmr +HELP                                              |
  |     Write this help message to standard output and exit. |
  |                                                          |
  | $ cmr +PCMODELS_VERSION                                  |
  |     Write the version number of the CMR program to       |
  |     standard output (e.g. 4.34) and exit. If CMR program |
  |     is not accessible for any reason, write 000.         |
  |     NOTE: The program version is different than the      |
  |           algorithm version.  The current version of the |
  |           algorithm (3.55) can not be retrieved          |
  |           programmatically.                              |
  |                                                          |
  | $ cmr +PCMODELS_ERRORTEXT                                |
  |     Write a list of English translations of all possible |
  |     CMR error levels to standard output and exit.        |
  |     Format is: $I<-{errorlevel}R;{translation}>|.        |
  |                                                          |
  | $ cmr +PCMODELS_TABLEOUTPUT                              |
  |     Set output format to verbose tables.                 |
  +----------------------------------------------------------+
  
  

• clogp, cmr requires TDT files, so first create a TDT file from the SMILES file

  smi2tdt SAMPLE.medchem.smi SAMPLE.medchem.tdt

  sun1% smi2tdt SAMPLE.medchem.smi >SAMPLE.medchem.tdt 
  sun1% more SAMPLE.medchem.tdt
  
  $SMI<NCCc1ccc(O)c(O)c1>
  PCN<DOPAMINE>
  |
  $SMI<CN1C(=O)N(C)C(=O)C(N(C)C=N2)=C12>
  PCN<CAFFEINE>
  |
  $SMI<CCN(CC)C(=O)C1CN(C)C2CC3=CNc(ccc4)c3c4C2=C1>
  PCN<LSD>
  |
  ...
  

• generate clogp, cmr values into the SAMPLE.medchem.tdt file

  clogp SAMPLE.medchem.tdt > SAMPLE.medchemcp.tdt

  sun1% clogp SAMPLE.medchem.tdt>SAMPLE.medchemcp.tdt
  sun1% more SAMPLE.medchemcp.tdt
  
  $SMI<NCCc1ccc(O)c(O)c1>
  PCN<DOPAMINE>
  CP<0.169;-0P;4.62>
  |
  $SMI<CN1C(=O)N(C)C(=O)C(N(C)C=N2)=C12>
  PCN<CAFFEINE>
  CP<-0.057;-10P;4.62>
  P1<-0.07>
  |
  $SMI<CCN(CC)C(=O)C1CN(C)C2CC3=CNc(ccc4)c3c4C2=C1>
  PCN<LSD>
  CP<2.692;-0P;4.62>
  P1<2.95>
  |
  ...
  

  cmr SAMPLE.medchemcp.tdt > SAMPLE.medchemcpcr.tdt

  sun1% cmr SAMPLE.medchemcp.tdt >SAMPLE.medchemcr.tdt
  sun1% more SAMPLE.medchemcpcr.tdt
  

  font color=red $SMI<NCCc1ccc(O)c(O)c1> PCN<DOPAMINE> CP<0.169;-0P;4.62> CR<4.291;-0R;4.62> | $SMI<CN1C(=O)N(C)C(=O)C(N(C)C=N2)=C12> PCN<CAFFEINE> CP<-0.057;-10P;4.62> P1<-0.07> CR<4.990;-0R;4.62> | $SMI<CCN(CC)C(=O)C1CN(C)C2CC3=CNc(ccc4)c3c4C2=C1> PCN<LSD> CP<2.692;-0P;4.62> P1<2.95> CR<9.682;-0R;4.62> | $SMI$lt;N12CCC36C1CC(C(C2)=CCOC4CC5=O)C4C3N5c7ccccc76> PCN<STRYCHNINE> CP<1.658;-10P;4.62> P1<1.93> CR<9.233;-0R;4.62> | ...

• Interpret error codes in results.

  clogp +PCMODELS_ERRORTEXT

  sun1% clogp +PCMODELS_ERRORTEXT    
  $I<-0P;All fragments measured>|
  $I<-10P;Trusted fragment value used>|
  $I<-20P;Estimated fragment value used>|
  $I<-30P;Approximated fragment value used>|
  $I<-31P;Benzyl approximation used>|
  $I<-32P;Vinyl approximation used>|
  $I<-33P;New approximated fragment value used>|
  $I<-40P;A priori fragment value used>|
  $I<-41P;Benzyl approx. based on a priori value>|
  $I<-42P;Vinyl approx. based on a priori value>|
  $I<-43P;Other a priori fragment value used>|
  $I<-50P;Warning, hard-to-estimate structure>|
  $I<-51P;Very high LogP unrealistic in nature>|
  $I<-52P;"X/Y-C-C-Y" excessive structure>|
  $I<-54P;Possibly low due to hydrophillic overlap>|
  $I<-55P;Valid estimate for steroid>|
  $I<-56P;Valid estimate for alkaloid>|
  $I<-57P;Error uncertain for charged structures>|
  $I<-58P;(NEW) STRUCTURE CAUGHT IN SCREEN>|
  $I<-60P;Invalid due to missing fragment value>|
  $I<-70P;Apparent impossible structure>|
  $I<-71P;ClogP can't do disconnected structures>|
  $I<-72P;Apparent impossible structure>|
  $I<-80P;Invalid smiles input (fatal)>|
  $I<-90P;Null smiles input (fatal)>|
  

  Any values with error codes >60 are invalid. Values with error codes >40 and <60 are approximate.

• Interpret error codes in results

  Get list of Error Codes

  cmr +PCMODELS_ERRORTEXT

  sun1% cmr +PCMODELS_ERRORTEXT
  $I<-0R;High confidence CMR estimate>|
  $I<-40R;CMR uncertain due to missing CONJUGATION>|
  $I<-42R;CMR uncertain due to missing BOND value>|
  $I<-61R;INVALID CMR due to missing ATOM value>|
  $I<-71R;CMR can't do disconnected structures>|
  $I<-72R;UNKNOWN CMR error condition>|
  $I<-80R;UNKNOWN CMR error condition>|
  
  

  Any disconnected structures such as salts will have invalid cmr values.