Fragmenter

Version 5.8.2

Contents

• Introduction
• Fragmentation methods
• RECAP (Fragment)
• CCQ (MolFragment)
• Fragment statistics
• R-group decomposition

 

Introduction

Fragmenter is a product consisting of several loosely related tools:

• Fragment cleaves single bonds to generate molecular fragments. The cleavage rules can correspond to retro-chemical reactions in order to enhance synthetic accessibility (like RECAP method).
• CCQ fragmentation (MolFragment) is a fast and simple method by fragmenting along functional groups but not destroying them, so no rules, no labelling is needed. This method can help to estimate toxicity of the molecules.
• FragmentStatistics related to Fragment enables library analysis based on labelled fragments created by Fragmenter.
• R-group decomposition generates an R-group table from a combichem library and a given scaffold.

Fragmentation methods

Fragment, the RECAP method

The cleavage points on the fragments are labeled with the cleavage rules:

The default cleavage rules used by Fragmenter. It is typically used with the RECAP algorithm, but Fragmenter accepts any custom cleavage rules described by reaction equations.

An example fragmentation of tamoxifen (left), an oestrogen antagonist and atenolol (right), an anti-hypertension drug.

Fragmenter fragments molecules based on predefined cleavage rules. The cleavage rules are given in form of reaction molecules in the configuration XML.

By default, all non-ring bonds matching the cleavage bonds in the rules are cleaved. However, it is possible to provide a revision algorithm that forbids certain cuts depending on predefined criteria (e.g. the resulting fragment size, the structural environment of the bond, the number of cleaved bonds in the resulting fragments, etc.). Currently one such algorithm is implemented: the RECAP method.

The RECAP algorithm raises the following cleavage revision rules:

1. Never cut a hydrogen-connecting bond.
2. Never cut a bond connecting a ring-carbon and a hetero atom (optional).
3. Never cut ring bonds. (Fragmenter always keeps this rule, we add it here for completeness.)
4. Refuse a cut if any of the resulting fragments is on the specified Notlist.
5. Refuse a cut if the number of open bonds in any of the resulting fragments exceeds the specified limit.
6. Refuse a cut if the number of atoms in any of the resulting fragments is less than the predefined minimal atom count.

Read more about the RECAP method and Fragmenter.

MolFragment, the CCQ method

The CCQ terminology means that single bonds connecting two carbon atoms (CC) are cleaved if at least one of those carbons is connected to a heteroatom (Q).

This method differs from the RECAP method because it leaves the functional groups intact, so no labelling is needed. Additionally, it requires no rule definitions. CCQ generates all fragments with duplicate filtering and provides an option to define the maximum bond count to decrease the small chance of a combinatorial explosion in case of extra complex molecules.

The CCQ fragmentation of atenolol, an anti-hypertension drug.

Learn more about the CCQ method in the MolFragment page.

Fragment statistics

FragmentStatistics creates statistical results from the output of Fragment. The simplest usage is to remove duplicate fragments and sort fragments by occurrence, but FragmentStatistics can also sort fragments by molecule activity or other data read from the input molecules and stored together with the generated fragments.

A detailed explanation with examples is found in the FragmentStatistics document.

R-group decomposition

R-group decomposition is a special kind of substructure search that aims at finding a central structure - scaffold - and identify its ligands at certain attachment positions. The query molecule consists of the scaffold and ligand attachment points represented by R-groups. These R-groups are simple R-group atoms without R-group definitions in most cases.

Find details in the R-Group Decomposition document.