The LigPrep Process

The LigPrep process consists of a series of steps that perform conversions, apply corrections to the structures, generate variations on the structures, eliminate unwanted structures, and optimize the structures. Many of the steps are optional and are controlled by selecting options in the LigPrep panel or by specifying command-line options. The steps are outlined below. For each step, utilities that can be used to perform this task are also listed.

While the generation of ionization states and tautomers (Step 5 and Step 6 ) can be carried out with tools that are part of LigPrep, a separate product, Epik, can be used instead to perform these structural adjustments during a LigPrep run. Epik more rigorously adjusts the tautomerization and ionization states than separate ionizer and tautomerizer treatments .However, it is slower, taking on average around 1 second longer per output structure on a 2 GHz processor.

If the input structure file is in SD format or SMILES format, it is converted to Maestro format. Parities specified in the SD file are converted into chiralities, which are stored as properties in the Maestro file. A SMILES input file should have one SMILES pattern per line, which can be followed by an optional title string. (Utilities: sdconvert,smiles_to_mae)

Structures that have implicit hydrogen atoms may need to have hydrogen atoms added before the 3D structures can be minimized. (Utility: applyhtreat)

If structures have additional molecules included, such as counter ions in salts and water molecules, these may need to be removed. This step removes all but the molecule containing the most atoms from each structure. This step is run by default, but is an optional step.

Charged groups must be neutralized before ionization states can be generated. The neutralization is performed by adding or removing hydrogen ions. This step is run by default, but is an optional step. (Utility: neutralizer)

For some applications, it is important that all species that exist in a given pH range are available. In this step, various ionization states are generated for each structure. This step should be preceded by a neutralization step. It is not run by default. (Utility/program: epik, ionizer)

As with ionization, the tautomeric states with a significant population may be important for some types of calculations. This step generates various tautomers for each structure. It is not run by default. (Utility/program: epik)

In this step, structures that match specified conditions can be removed. The condition can be on a property, such as Molecular weight > 1000, or on the structure, such as the presence or absence of a specific functional group. This step is not run by default. (Utility: ligfilter)

Input structures given in 1D or 2D often have indicated chiralities, and 3D structures many need the chiralities inherent in the geometry retained. Unspecified chiralities must of course be assigned. This step identifies all chiral atoms in the structures and provides options to retain chiralities or generate additional stereochemical isomers with the same molecular formula. The step is not run by default. (Utility: stereoizer)

Generate 3D conformations for the structures using ConfGen technology and optionally minimize them (Program: confgenx Command Help).

If output in SD format was requested, the format conversion is performed. (Utility: sdconvert)