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Pharmacophore Alignment (version 0.1)

Defines the database of molecules that will be used to screen:

Reference Molecule:

Specify a subset of the available functional groups that are used in the alignment:

Change the tolerance for points to be matched in the alignment phase:

The lower this value, the more strict the matching between two pharmacophores will have to be before they can be aligned.

Merge pharmacophore points:

No normal information is included during the alignment:

Using this flag makes the pharmacophore models less specific but also less conformation-dependent.

Disable the use of hybrid pharmacophore points:

Using this flag will increase the number of pharmacophore points.

Add exclusion spheres into the optimization process instead of processing them afterwards:

When this flag is set, the exclusion spheres have also an impact on the optimization procedure.

No translational or rotational optimization will be performed:

Only structures with a score larger than this cutoff will be written to the files:

This value should be between 0 and 1.

With this option only a limited number of best scoring structures are written to the files:

0 means this option is deactivated

This option defines the used scoring scheme:

What this tool does

Align-it is a tool to align molecules according to their pharmacophores. A pharmacophore is an abstract concept based on the specific interactions observed in drug-receptor interactions: hydrogen bonding, charge transfer, electrostatic and hydrophobic interactions. Molecular modeling and/or screening based on pharmacophore similarities has been proven to be an important and useful method in drug discovery.

The functionality of Align-it consists mainly of two parts. The first functionality is the generation of pharmacophores from molecules (use the tool Pharmacophore generation if you want to store these for further use). Secondly, pairs of pharmacophores can be aligned (the function of this tool). The resulting score is calculated from the volume overlap resulting of the alignments.

Input

Example:

- database

 30 31  0     0  0  0  0  0  0999 V2000
    1.9541    1.1500   -2.5078 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    1.1377   -1.6392    2.1136 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   -3.2620   -2.9284   -1.0647 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7906   -1.9108    0.9092 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.2679   -0.2051   -0.3990 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0640    0.5139   -0.3769 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7313    0.7178   -0.0192 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4761   -0.6830   -1.1703 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6571   -0.2482   -0.1795 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0382    1.4350    0.0081 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3728    1.8429    0.7234 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6797    2.5600    0.7506 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3470    2.7640    1.1083 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5353    0.3477   -1.0918 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1740   -0.8865    0.9534 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8480   -1.8749   -0.3123 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9124    0.3058   -0.8739 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5511   -0.9285    1.1713 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4203   -0.3324    0.2576 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7086   -0.9792   -1.8930 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3614   -0.4266   -1.7676 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0861   -1.1146   -0.6780 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0812    1.2885   -0.2604 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.6569    2.0278    1.0167 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4382    3.2769    1.0511 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0683    3.6399    1.6868 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.6037    0.7654   -1.5758 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.9635   -1.4215    2.0480 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.4925   -0.3651    0.4274 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5025   -3.7011   -0.5102 H   0  0  0  0  0  0  0  0  0  0  0  0

- cutoff : 0.0

Output

The format of the output file is shown in the table below:

Column	Content
1	Id of the reference structure
2	Maximum volume of the reference structure
3	Id of the database structure
4	Maximum volume of the database structure
5	Maximum volume overlap of the two structures
6	Overlap between pharmacophore and exclusion spheres in the reference
7	Corrected volume overlap between database pharmacophore and reference
8	Number of pharmacophore points in the processed pharmacophore
9	TANIMOTO score
10	TVERSKY_REF score
11	TVERSKY_DB score

Example:

- aligned Pharmacophores

    3033
    HYBL    -1.98494    1.9958    0.532089    0.7    0    0    0    0
    HYBL    3.52122    -0.309347    0.122783    0.7    0    0    0    0
    HYBH    -3.262    -2.9284    -1.0647    1    1    -3.5666    -3.7035    -1.61827
    HDON    0.2679    -0.2051    -0.399    1    1    -0.076102    -0.981133    -0.927616
    HACC    -2.7906    -1.9108    0.9092    1    1    -2.74368    -1.94015    1.90767
    $$$$

Cite

Silicos-it - align-it