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MMP Calculate Maximum Cuts

DeprecatedVernalis Chemistry Matched-Molecular Pairs extension for KNIME Workbench version 1.27.2.v202010191232 by Vernalis (R&D), UK

This node pre-filtes molecules by viabilty in the specified MMP schema. The user can specify the number of cuts to be made (1 - 10), and whether Hydrogens should be added (for 1 cut only).

A variety of fragmentation options are included:

  1. "All acyclic single bonds" - Any acyclic single bond between any two atoms will be broken. This is the most exhaustive approach, but can generate a large number of pairs (rSMARTS: [*:1]!@!=!#[*:2]>>[*:1]-[*].[*:2]-[*])
  2. "Only acyclic single bonds to rings" - Single acyclic bonds between any atoms will be broken, as long as at least one atom is in a ring (rSMARTS: [*;R:1]!@!=!#[*:2]>>[*:1]-[*].[*:2]-[*]).
  3. "Only acyclic single bonds to either rings or to double bonds exocyclic to rings" - single acyclic bonds between any atoms will be broken, as long as 1 atom is either in a ring, or in a double bond exocyclic to a ring, with the other end in the ring (rSMARTS: [*:1]!@!=!#[*;!R0,$(*=!@[*!R0]):2]>>[*:1]-[*].[*:2]-[*])
  4. "Only single bonds to a heteroatom" - Single acyclic bonds between any two atoms, at least one of which is not Carbon will be broken. Included to mirror C-X bond breaking chemistry prevalent in modern drug discovery (e.g. SNAr, Reductive Aminations, Amide formations etc. See Ref. 2) (rSMARTS: [!#6:1]!@!=!#[*:2]>>[*:1]-[*].[*:2]-[*])
  5. "Non-functional group single bonds" - This reproduces the fragmentation pattern used in the original Hussein/Rea paper (See footnote 24, Ref. 1), and also used in the RDKit Python implementation (Ref 3) (rSMARTS: [#6+0;!$(*=,#[!#6]):1]!@!=!#[*:2]>>[*:1]-[*].[*:2]-[*])
  6. "User defined" - The user needs to provide their own rSMARTS fragmentation definition, following the guidelines below.

Guidelines for Custom rSMARTS Definition

  • '>>' is required to separate reactants and products
  • Products require '[*]' to occur twice, for the attachment points (the node will handle the tagging of these)
  • Reactants and products require exactly two atom mappings, e.g. :1] and :2] (other values could be used).
  • The atom mappings must be two different values
  • The same atom mappings must be used for reactants and products
rSMARTS not conforming to these guidelines will be rejected during node configuration.

The algorithm is implemented using the RDKit toolkit.

This node was developed by Vernalis Research . For feedback and more information, please contact knime@vernalis.com

1. J. Hussain and C Rea, " Computationally efficient algorithm to identify matched molecular pairs (MMPs) in large datasets ", J. Chem. Inf. Model. , 2010, 50 , 339-348 (DOI: 10.1021/ci900450m ).

2. S. D. Roughley and A. M. Jordan " The Medicinal Chemist’s Toolbox: An Analysis of Reactions Used in the Pursuit of Drug Candidates ", J. Med. Chem. , 2011, 54 , 3451-3479 (DOI: 10.1021/jm200187y )

3. G. Landrum " An Overview of RDKit " (http://www.rdkit.org/docs/Overview.html#the-contrib-directory) (section entitled 'mmpa')

Options

Select Molecule column
Select the column containing the molecules
Select the Fragmentation Type
Select the required fragmentation option
User rSMARTS
The optional user-defined rSMARTS (see above for details)
Allow 2 cuts along single bond giving a single bond as 'value'?
If selected, for the 2 cuts case, 1 bond can be cut twice, allowing a 'value' of [*:1]-[*:2] (i.e. a 'bond') to be formed
Add H's for n=1
If checked, the value returned will account for n=1 being allowed if H's are added

Input Ports

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Molecules for filtering

Output Ports

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Incoming table with the maximum number of cuts according to the selected schema calculated. Molecules which could not be parsed in RDKit will return missing values.

Best Friends (Incoming)

Best Friends (Outgoing)

Installation

To use this node in KNIME, install Vernalis KNIME Nodes from the following update site:

KNIME 4.2

A zipped version of the software site can be downloaded here.

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