CombiGlide Reagent Preparation

Reagent preparation ensures that the input structures are all-atom, 3D structures, and that they have the appropriate information stored with them to construct the molecules that are used in screening or are added to the library. Apart from 2D-to-3D conversion and structure variation and cleanup, which is performed by LigPrep, the main task in this node is to select a reagent type (a functional group) and to identify the bond in the functional group that is replaced when the reagent is added to the core. The reagent preparation job attempts to identify the selected functional group in each structure. Structures that match are then prepared using LigPrep. The structure source does not therefore need to contain only structures that have the desired functional group: structures that don't are filtered out. Duplicates are not filtered out, however, so you should ensure that the input file does not contain duplicates. The output file contains the prepared reagents. There might be several output structures per input structure if the molecule can exist in several low-energy forms. You must run this node for each reagent type that will be used in combinatorial screening or combinatorial library enumeration.

Backend implementation

Options

Column containing input

Choose the input column containing the reagents

Functional group to identify

Ionize

Protonate or deprotonate the reagents to represent the actual form in water in the given pH range. If deselected, the structure's initial ionization state is retained.

Generate Tautomers

Select this option to generate tautomers of the input structures. Ionized structures might have a different tautomeric form from the unionized structures.

Use Epik for ionization and tautomerization

Select this option to use Epik for ionization and tautomerization rather than the ionizer and the tautomerizer.

Generate stereoisomers

Enter the number of stereoisomers to generate. If the input structures are 2D and have chiral centers but do not have chirality information, you should ensure that the number specified covers the possible combinations.

Generate low-energy ring conformations

If the input structures contain rings that can exist in more than one low-energy conformation, enter the number of likely low-energy conformations in this text box. Ring conformations are not searched during docking, so the conformations must be set up beforehand.

Input Ports

Input data table containing molecules in Maestro format

Output Ports

Molecules in Maestro format

Views

Log output of CombiGlide Reagent Prep

Log output of CombiGlide Reagent Prep

Best Friends (Incoming)

• Fragments from Molecules (100 %) 
• Molecule-to-MAE (< 1 %) 

Best Friends (Outgoing)

• MAE-to-SD (100 %) 

Installation

To use this node in KNIME, install Schrödinger Nodes for Suite2019-1 from the following update site: