2.2 Defining a spacer

A spacer in NEWLEAD can have more than one connection to two fragments -- think of the ortho, meta and para disubstitutions of benzene. It can also have more than one conformation. A connection on a NEWLEAD spacer is uniquely defined by a pair of hydrogen atoms.

stand alone use Start the program vectors at the UNIX prompt. vectors puts the connection data in an ASCII file to be read by the program nfe using the Merge command. vectors creates also one or more coordinate files in Columbia format to be read by NEWLEAD. The following options are used

  1. -i input file with the coordinates of the spacer. You can use the following formats: Columbia, CAR-archive, and MOL2. Multiple conformations can be used, except for a MOL2 file. Default: spacer.dat
  2. -o ASCII output file to be used with the nfe program. Default: vectors.dat
  3. -n name of the spacer, and root name for the coordinate files. Default: root name of the input file (e.g., my_spacer.car -> my_spacer)
  4. -l list of H-atoms defining pairs of connections, in the form "l,k n,m ..."
  5. -m indicates a multi-conformation input (not usable for MOL2 files)
  6. -a append the results to the output file defined above.


vectors -l "7,16 7,17" \
-i naphthalene.mol2 \
-o vect.dat -a

two pairs are defined, and appended to the file vect.dat. The coordinate file naphthalene.dat is created in Columbia format

vectors -l "6,15 6,16" -m \
-i butylamine.car \
-n 1_aminobutane

two pairs are defined for several conformations. The data is written to the default output vectors.dat. N Columbia files are written out, one for each conformation:


NOTE: if the -l keyword is omitted, the program vectors lists all possible connections and prompts the user to accept or discard each of them.

Accelrys interface The BCL macro NEWLEAD_Vectors in the menu Measure of InsightII helps you define your own spacers -- possibly with multiple connections and conformations -- by means of graphical, point-and-click operations.

NEWLEAD_Vectors creates an ASCII file with all the needed data for the spacer. This file is then read in by the program nfe to store the spacers permanently in a NEWLEAD spacer library. NEWLEAD_Vectors also creates the spacer data files that must be put in the directory $NEWLEAD_ROOT/bridges for the default library or in a directory of your choice if you are defining a custom library.

NEWLEAD_Vectors is used in two stages

  1. collect all pairs of H-atoms defining each connection
  2. define the name of the spacer, check for multiple conformations and output the data on disk

Fig. 1

When first activated (see Fig. 1), NEWLEAD_Vectors is ready to collect pairs of H-atoms for a single spacer displayed on the screen. To proceed, simply pick H-atoms, two at the time, on the spacer. The name of each H-atom is displayed in the two fields "Atom_1" and "Atom_2". The distance between the two H-atoms is also displayed, mostly to help avoid picking the same pairs twice (it is however possible to have an individual H-atom in more than one pair).

The spacer can also be in many conformations. In such case, you must have all the conformers in an assembly, and pick pairs of H-atoms on only one conformer (it is best to blank all except one).

After you picked all connection pairs of interest, click the "End definition" button. This activates the second and last stage of NEWLEAD_Vectors (see Fig. 2). To complete the operation, use the following buttons and text fields

  • Multi Conformation button
    check if your spacer has more than one conformation
  • Sort by Angles button
    please leave as it is
  • Spacer Name field
    fill in the name of the spacer. It is important to choose a unique name carefully because it will be used by NEWLEAD in all runs. Use only letters, numbers and the underscore '_'; do not use blanks or punctuation marks. The default is the OBJECT name defined by InsightII, in lowercase letters
  • Vector File field
    fill in the name of the ASCII file to store the data defined so far. Remember this name because it is needed later to actually add the spacer to the library. The default is "vectors.dat"
  • Append to File button
    check if you want to add more data at the end of the "Vector File" defined above. This is useful if you plan to define more than one spacer during an InsightII session
  • Start nfe button
    check if you want to start the program nfe .

Finally, click the "Execute" button. The following events take place

  • the "Vector File" is created, usually with the default name vectors.dat
  • for a spacer in a single conformation, a file <spacer>.dat is created, where <spacer> is the name given above in the "Spacer Name" field. For many conformers, these files are created


    where <spacer> is again the name given above and N is total number of conformations.
    These files must be put into the directory $NEWLEAD_ROOT/bridges to be accessible to NEWLEAD
  • if applicable, the program nfe is started. Typically, you will then activate the command "Merge..." of nfe, to read in the "Vector File" and add the spacers just defined to a spacer library.

After the above operations are completed (you must also quit nfe, if you chose to use it), you have the options to restart the process by checking off the "End Definition" button of NEWLEAD_Vectors (see Fig. 2). You can then pick connection pairs for another spacer, and then complete again the second stage described above. This time, it will be useful to check the "Append to File" button to add the data for the new spacer at the end of the previous "Vector File". In this way, the data for all the new spacers defined in one session will be collected in a single file.

Now that you have defined all the spacers needed, you must make the data available to NEWLEAD. This is what you need to do

  • store the spacer data files <spacer>.dat
  • activate the program nfe (if you didn't do it already), go to the module "Spacers...", and use the command "Merge..." to add the data defined in the file "Vector File" to the spacer library
  • optionally, add the name of the new spacers to the appropriate groups by using the module "Groups..." of nfe.



Fig. 2

NOTE: currently, it is not possible to define a fused-ring spacer with NEWLEAD_Vectors.