两种药效团模型搭建

How to set up a 3D QSAR Pharmacophore Generation run

The 3D QSAR Pharmacophore Generation protocol generates SAR hypothesis models (pharmacophores) from a set of ligands for which activity values on a given biological target have been measured.

Note.To ensure proper exploration of the ligand conformational and pharmacophoric space, it is recommended that you run the Diverse Conformation Generation protocol prior to running this protocol.

The input ligands need the following molecular properties: Activ(representing the ligand's tested activity) and Uncert(set to 3.0by default, representing the ratio range of uncertainty in the activity value). Molecular properties can be added using the Add Attribute dialog.

To set up a 3D QSAR Pharmacophore Generation protocol:

1.Load the Pharmacophore | 3D QSAR Pharmacophore Generation protocol from the

Protocols Explorer. The parameters display in the Parameters Explorer.

2.On the Parameters Explorer, click in a cell for the Input Ligands parameter

and click the button to specify the ligand source on the Specify Ligands

dialog. On the dialog, select all ligands from a Table Browser, a 3D Window, or a file. The molecular properties Activ and Uncert should be set for these molecules. If they are not set, they will be assigned a default value of 0.0 and 3.0, respectively.

3.Specify the pharmacophore features using the Features parameter. Selecting

this parameter opens the Select Features dialog . On the dialog, you may select the desired pharmacophore features and the minimum and maximum values desired for the final pharmacophores.

4.Set the remaining parameters as desired. Parameters presented in red are

required.

Note.If using the Maximum Excluded Volumes parameter in this protocol, we recommend using a value of 5.

Note. When generating SAR pharmacophores, which include excluded volumes, the algorithm looks for differences in the steric bulk between the most active compound, and the inactive compounds. However, it is possible to explicitly specify which compounds to use for this analysis. This is done by adding a Principal property to the input ligands. For normal SAR hypothesis model generation, this property is ignored. When using the HypoRefine algorithm to add excluded volumes, however, these values can be used to determine which molecules are used when placing the excluded volumes. Values that are provided will be used as follows:

0,NULL: Ignore compound in excluded volume addition

1 : Treat compound as Inactive.

2: Treat compound as Active.