Make Ligand Coordinate and Restraint Dictionaries with Acedrg

The Make Ligand task uses the program ACEDRG to derive stereo-chemical information about monomers/ligands (or small molecules). ACEDRG can derive “ideal” bond lengths, angles for an unknown monomer/ligand. It also generates information about planar groups and stereo-chemical properties in the monomer/ligand. The minumum information Acedrg requires is element types of atoms in the monomer/ligand, and the basic bonding pattern in the monomer/ligand, such as atom connnections and bond-orders

Input

Figure 1: Main *Make Ligand* options

Figure 1: Main Make Ligand options

Make Ligand accepts SMILES strings (either as a file or pasted text) and MOL files as input. Also Lidia: Coot’s Ligand Builder can be used to generate the input for ACEDRG The choice of input method is selected using drop-down menu(1).

If the menu is set to “a MOL file” or “a SMILES file”, then a file of the appropriate type must be loaded/selected in the data selector menu(2).

If the menu is set to “a SMILES string”, then a text box is shown into which a SMILES string may be typed/pasted(3).

Clicking the Run button will then run ACEDRG with the MOL or SMILES as input. .. figure:: lidia.png

alt:

Figure 2:Lidia

Figure 2:Lidia

If the menu is set to “a sketch”, then when the “Run” button is pressed, the first thing that will happen is that Lidia(Figure 2) will be launched. When “a sketch” is selected an option to provide a starting point for the sketch is also shown. The starting point input may be a MOL file or output from a previous Make Ligand job. Lidia is a molecular sketcker provided by COOT. It allows the user to create 2D (with stereo-isomer information) sketches of molecules. The output of Lidia is subsequently passed to ACEDRG by the Make Ligand task. In order for this to happen correctly, the user must click Apply(6) then Close(7) when finished sketching with Lidia.

The 3-letter code to be given to the monomer should be typed into text box(4)

Figure 3: Main *Make Ligand* options with SMILES input box

Figure 3: Main Make Ligand options with SMILES input box

Although ACEDRG attempts to name atoms sensibly, it is sometimes desirable to try to match the atom names to those in a similar structure. For instance, if the ligand to be generated contains a large group of atoms in common with those of another ligand, it can be useful to make sure the same atoms have the same names. This can be done by changing the atom matching menu(5) from nothing to either: a specific 3-letter code, in which case a text box appears into which the 3-letter code of the existing reference ligand should be typed; or use dictionary in which case a CCP4i2 Geometry dictionary data selector appears - an existing dictionary in the CCP4i2 database or dictionary file should supplied; or all monomers in which case the whole CCP4/refmac5 monomer library is searched for a matching group of atoms.

Advanced options

Figure 4:*Advanced options*

Figure 4:Advanced options

This task has one advanced option - the number of random RDKIT starting structures. The task will attempt to generate a sensible geometric conformation of the generated ligand atoms, in addition to the restraint dictionary. The RDKIT library is used to optimize the geometry. In order to avoid finding a local minimum, several initial arrangements of atoms are optimized; the optimized geometry with the lowest energy of them all is accepted. The more initial conformations are used, the more likely a better optimal geometry will be found.

Results

Figure 5:*Report - 2D picture*

Figure 5:Report - 2D picture

The report is very simple and consists of 3 parts:

A 2D depiction of the generated ligand and the corresponding SMILES string.

Figure 6:*Report - 3D picture*

Figure 6:Report - 3D picture

A 3D representation of the optimized geometry

Figure 7:*Report - Input and output files*

Figure 7:Report - Input and output files

A list of output data and any input data files.