PharmaGist Help

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[About] [WebServer] [FAQ] [Help / Getting Started] Contact: ppdock@tau.ac.il

Input Fields:

Input Molecules: the server accepts up to 32 input molecules in mol2 format. The user can upload the molecules in a single mol2 file or in a zip of several mol2 files. Notice that though the PharmaGist server treat the molecules as flexible, it may only change their torsion angles. Bonds length and bonds angle must be correct in the input file/s. Hydrogen atoms should also be explicitly specified. An example for an input Mol2 file can be found here .

No. of Output Pharmacophores: number of the candidate pharmacophores that will be shown for each number of input molecules.

E-Mail Address: the link with the results of your request is sent to this address. Using this link you can view the results. The results are kept on the server for at least a month, so they can be viewed with the link later again.

Advanced Options:

Key-Molecule: the user can set the first ligand in the input to serve as a key/pivot molecule. In this case all the other ligands are aligned onto it and all the pharmacophore candidates include this key ligand. By default, the algorithm iteratively selects each input ligand to serve as a key/pivot. This molecule can be the ligand with highest affinity to the receptor or the one with the lowest number of rotatable bonds.

Min no. of features in pharmacophore: the minimal number of spatially distinct features in the reported pharmacophore candidates.

Feature weighting options: there are four feature types currently supported by the algorithm: (i) aromatic ring, (ii) hydrogen bond donor/acceptor, (iii) charge (anion/cation) and (iv) hydrophobic. The user can modify the weights of the features in the scoring function of the algorithm. For example, if the user knows that the interaction with the target receptor is mostly hydrophobic, he is encouraged to increase the weight assigned to an hydrophobic feature.

User Defined Feature: Additional feature type can be defined by the user. A feature file in the following format has to be prepared. Each line in the feature file corresponds to one input molecule specified by its filename. Next user defined features are listed separated by semicolon. The atoms of the features are identified by their atom number in mol2 file. In the example below, three input molecules are assigned with user defined features. adinazolam.mol2 is assigned with two features located on atoms number 13 and 17, amiodarone.mol2 is assigned with two features located on atoms number 28 and 30 and azelastine.mol2 is assigned with one feature located on atom number 24.

adinazolam.mol2 13;17
amiodarone.mol2 28;30
azelastine.mol2 24

In addition, the user can define a feature based on a group of atoms. In this case, the spatial 3D point associated with this feature will be an average of the atom group coordinates. To specify a group of atoms in the feature file, just type their numbers, separated by comas. For example:

adinazolam.mol2 13,14,15;17

This defines two features, the first one is an average of atoms 13,14,15 and the second one is on atom number 17.

Server Output:

The main output contains several tables.

The upper table presents the names of the input molecules along with their number of atoms and their assigned physico-chemical features. In addition, the user can click on "view details" and the Jmol window with molecules and their features will be shown. The user can select/unselect each input molecule and the associated features by clicking the relevant checkbox.

Input Molecules view details: visualization of the detected features

#	Molecule	Atoms	Features	Spatial Features	Aromatic	Hydrophobic	Donors	Acceptors	Negatives	Positives
1	streptavidin_pharma_1.mol2	39	13	12	2	4	1	5	1	0
2	streptavidin_pharma_2.mol2	30	10	9	2	1	1	5	1	0
3	streptavidin_pharma_3.mol2	35	11	10	2	0	1	7	1	0
4	streptavidin_pharma_4.mol2	33	11	10	2	2	1	5	1	0
5	streptavidin_pharma_5.mol2	33	10	9	3	0	1	5	1	0

The next tables give a summary of the results. Each result table presents the highest scoring pharmacophore candidates shared by a specific number of input molecules. These tables are sorted in descending order from the table for the largest number of molecules to the one for three molecules. The pharmacophore candidates in each table are sorted in the descending order by their scores. In addition, it is possible to sort these tables by score. Besides the score, for each pharmacophore candidate the following data appears: (i) the name of the participating molecules, (ii) the number of common features and their type distribution, and (iii) a link to a page describing the pharmacophore candidate. For example:

Number of Aligned Molecules: 5

Score	Jmol	Features	Spatial Features	Aromatic	Hydrophobic	Donors	Acceptors	Negatives	Positives	Molecules
37.250	jmolScript_5_1.html	7	7	2	0	0	4	1	0	streptavidin_pharma_5.mol2 streptavidin_pharma_1.mol2 streptavidin_pharma_2.mol2 streptavidin_pharma_3.mol2 streptavidin_pharma_4.mol2
32.917	jmolScript_5_2.html	6	6	2	0	0	3	1	0	streptavidin_pharma_3.mol2 streptavidin_pharma_1.mol2 streptavidin_pharma_2.mol2 streptavidin_pharma_4.mol2 streptavidin_pharma_5.mol2
25.786	jmolScript_5_3.html	4	4	2	0	0	2	0	0	streptavidin_pharma_3.mol2 streptavidin_pharma_1.mol2 streptavidin_pharma_2.mol2 streptavidin_pharma_4.mol2 streptavidin_pharma_5.mol2
22.134	jmolScript_5_4.html	4	3	2	0	1	1	0	0	streptavidin_pharma_1.mol2 streptavidin_pharma_2.mol2 streptavidin_pharma_3.mol2 streptavidin_pharma_4.mol2 streptavidin_pharma_5.mol2

Number of Aligned Molecules: 4

Score	Jmol	Features	Spatial Features	Aromatic	Hydrophobic	Donors	Acceptors	Negatives	Positives	Molecules
41.250	jmolScript_4_1.html	9	8	2	0	1	5	1	0	streptavidin_pharma_3.mol2 streptavidin_pharma_1.mol2 streptavidin_pharma_2.mol2 streptavidin_pharma_4.mol2

Number of Aligned Molecules: 3

Score	Jmol	Features	Spatial Features	Aromatic	Hydrophobic	Donors	Acceptors	Negatives	Positives	Molecules
41.885	jmolScript_3_1.html	10	9	2	1	1	5	1	0	streptavidin_pharma_2.mol2 streptavidin_pharma_1.mol2 streptavidin_pharma_4.mol2
41.875	jmolScript_3_2.html	10	9	2	1	1	5	1	0	streptavidin_pharma_4.mol2 streptavidin_pharma_1.mol2 streptavidin_pharma_2.mol2
15.502	jmolScript_3_3.html	3	3	2	1	0	0	0	0	streptavidin_pharma_1.mol2 streptavidin_pharma_2.mol2 streptavidin_pharma_4.mol2

Finally, there is a link to a table that presents the best pairwise alignment result for any pair of input molecules.

View Best Pairwise Alignments

For each pharmacophore candidate the server provides an additional page with a comprehensive description that can be accessed through a link from the tables in the main output page. The page consists of three parts: (i) a summary of the attributes of the pharmacophore at the top, (ii) a Jmol display on the right, and (iii) a display control panel on the left.

Score	Features	Spatial Features	Aromatic	Hydrophobic	Donors	Acceptors	Negatives	Positives
37.250	7	7	2	0	0	4	1	0

Molecule Name	Show Molecule:	Show Features:
streptavidin_pharma_5*
streptavidin_pharma_1
streptavidin_pharma_2
streptavidin_pharma_3
streptavidin_pharma_4

* pivot molecule

Download Pharmacophore and Alignment File

The summary part contains the score of the pharmacophore candidate, its number of features and their physico-chemical types. By default, the Jmol display shows the pharmacophore (spacefill model) and the multiple flexible alignment that yields it (wireframe model). The color coding of the features in the display is by their physico-chemical types and it is as in the summary part of the page at the top. The display control panel contains one row for each molecule in the alignment. In each raw, besides the name of the controlled molecule, which is colored as in the Jmol display, two checkboxes are given. The first checkbox allows the user to show/hide the controlled molecule in the display and the second checkbox controls the display of the molecule's features. In addition, the user can show/hide the pharmacophore in the display using the checkbox at the top of the summary part.