The OMEGA distribution includes flipper, a utility program for enumerating stereocenters in a molecule. We have taken the philosophy that conformer generation and stereochemistry enumeration are related but distinct problems. Thus we provide flipper as part of the OMEGA product, but not as part of the same executable.

The current version of flipper can handle enumeration of R/S stereochemistry (including N and S stereochemistry) as well as cis/trans stereochemistry. flipper uses graph algorithms to determine which atoms are stereocenters. If a stereocenter has a designated stereochemistry, by default flipper does not change the stereochemistry. However, if a stereocenter does not have a specified stereochemistry, flipper will enumerate both stereochemistry states of the stereocenter.

Many common file formats are limited in their ability to fully express stereochemistry without resorting to Cartesian coordinates. This can lead to ambiguity in whether a particular conformer is supposed to represent a racemic mixture or an isolated stereoisomer. SD file format is better than most formats. It allows designation of R, S, or racemic on each tetrahedral stereocenter independent of the particular conformation. However, SD format is not as robust for cis/trans stereochemistry. Isomeric SMILES is the only common file format which allows complete specification of R/S and cis/trans stereochemistry. In fact, although flipper does not currently support higher orders of stereochemistry, the isomeric SMILES format is capable of handling them. For this reason, flipper output is limited to SD format (.sdf or .mol) and isomeric SMILES format (.ism). OpenEye OEBinary format, like isomeric SMILES, is capable of fully specifying stereochemistry, however, isomeric SMILES is more efficient for compounds without any data beyond the title and connection table.

The flipper process can also be done with OMEGA using the -flipper flag.

Input dimensionality

flipper is designed for use prior to 3D coordinate generation. So 2D or 1D (SMILES) input is normally expected. Input files containing 3D coordinates are handled, but the 3D coordinates are ignored and not transferred to the output.

Example Commands

Below are three example flipper executions. Each example is followed by a brief description of the parameter’s effects. Sample data files can be found in the data directory.

prompt> flipper -in drugs.smi -out enumerated.ism

This execution will examine each stereocenter in drugs.smi. If the stereocenter does not have a specified stereochemistry, flipper will generate molecules with each of the stereochemistry states at each stereocenter.

prompt> flipper -in drugs.smi -out enumerated_forceflip.ism -forceflip true

This execution will differ from the first in that all stereocenters will be enumerated, regardless of whether the stereochemistry is specified in the input file.

prompt> flipper -in drugs.smi -out enumerated_maxcenters6.ism -maxcenters 6

In this execution, flipper will exhaustively enumerate all unspecified stereocenters in molecules with up to 6 stereocenters. For molecules with more than 6 stereocenters, a random set of 64 isomers will be generated from the larger set of potential stereoisomers.

Command Line Help

A description of the command line interface can be obtained by executing Flipper with the –help option.

> flipper --help

will generate the following output:

Help functions:
  flipper --help simple      : Get a list of simple parameters
  flipper --help all         : Get a complete list of parameters
  flipper --help defaults    : List the defaults for all parameters
  flipper --help <parameter> : Get detailed help on a parameter
  flipper --help html        : Create an html help file for this program
  flipper --help versions    : List the toolkits and versions used in the application

Required Parameters


File containing one or more molecules for which stereoisomers will be generated

Optional Parameters


Output molecule file name. The output file format is limited to OEB, isomeric SMILES (.ism and .smi) or SD format since these are the only formats which fully specify stereocenters without the need for three-dimensional coordinates.


Molecule names file corresponding to the input file.


Prefix to use to name output files.


Type of progress to show on screen during run.


The -enumNitrogen string flag controls the behavior of FLIPPER with respect to enumeration of nonterminal nitrogens. Any nitrogen with pyramidal geometry in the initial model of the input molecule, and having no more than two ring bonds is considered by OMEGA to be ‘invertible’. FLIPPER will enumerate all possible puckers if the -enumNitrogen flag is set to true. [default = false] [Aliases: -en]


This parameter forces flipper to modify all of the stereocenters in a molecule. If -enumSpecifiedStereo is false (the default), FLIPPER only enumerates stereocenters which do not already have a specified stereochemistry. [default = false] [Aliases: -forceflip]


Obviously, the number of molecules generated by enumerating the stereocenters is \(2^N\), where N is the number of stereocenters. In some instances, this may be larger than is desired. The -maxCenters parameter indicates the maximum number of stereocenters which will be fully enumerated. If a molecule has more than -maxCenters stereocenters, flipper will randomly enumerate 2^(maxCenters) instances from the full set of potential isomers. [default = 12][Aliases: -maxcenters]


Add wart to title of each stereoisomer. [default = false]


Enumerate bridgehead stereocenters. [Default = false]


Enumerate E/Z stereocenters only. [Default = false]


Enumerate R/S stereocenters only. [Default = false]