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Diversity

Diversity Analysis of Pharmacophoric Properties

General remarks

Pharmacophoric properties of a molecule depend on its pharmacophores and on their mutual spatial arrangement, i.e. on its conformation. In this generality Moloc can compare molecules in given conformations by a 3d-algorithm, that can be utilized interactively (mch/d) or with the batch program M3dsml (see documentation).
A more summarized (2d-) description is provided by Moloc's concept of topological pharmacophores that attributes to a molecule a single description and thus allows to compare two molecules by a single similarity value. This tutorial deals with this approach. We assume that in a combinatorial chemistry reaction a particular ligand substitution is achieved by reaction of a central scaffold with various aldehydes. This tutorial describes the assessment of pharmacophoric diversity of a set of aldehydes. An example set is provided by the file moloc/dat/aldhd.mab. For theoretircal background on topological pharmacophores see: Topological Pharmacophore Description of Chemical Structures using MAB-Force-Field Derived Data and Corresponding Similarity Measures.

Generate a file of Rooted Topological Pharmacophores

Calculation of the Pharmacophoric Similarity Matrix

Generation of the Similarity Tree

To analyze the similarity file return to Moloc where we still find ourselves in diversity menu 'dvrs' (mch/d). Now the display shows the similarity tree. The stem starts at similarity zero and then branches with increasing similarity values, until at similarity one its leaves represent the individual compounds.

Diversity Analysis

The purpose of diversity analysis is to come up with a set of a desired number of entries, which show a maximum amount of pharmacophoric diversity. For that purpose the options s, l, z allow to split up the tree in several subbranches, what we exemplify for the case 'l'.

Similarity Analysis

Similarity analysis applies to cases where a entry has desirable properties and further entries with similar (or hopefully better) properties are required. The branch display menu is meant to facilitate inspection of and selection from individual branches and provides the options: