CHUCKLES, CHORTLES and CHARTS

Daylight's first languages for combinatorial chemical mixtures. These languages have been incorporated into the Database package and the Monomer Toolkit.

Combinatorial chemistry was the inspiration for the Daylight "Monomer" representation of chemical structures. Storing and searching chemical structures, not as individual molecules, but as a part of a combinatorial library synthesized as a mixture is the problem which these combinatorial library languages address.

Combinatorial libraries have a synthetic design, the "Monomer" representation may have no synthetic connection, but rather a chemical information systems representation to facilitate storage and retrieval. In the Daylight system a combinatorial library can be represented in terms of monomers. The Monomer table is constructed and Monomers and Monomer Sets which are used to describe chemical mixtures stored in a database.

Monomer- "molecular chuck"-- a piece of a molecule that is typically more than one atom but less than a
whole molecule. It has three properties: a symbol, a SMILES and a description.

Left-to-right orientation is important

Monomer definitions need not represent valid molecules

Monomer definition SMILES is interpreted in the larger SMILES context(e.g. atom order)

Unmatched ring closures are acceptable

EXAMPLES

Monomer Table

Symbol	Definition	Description
Ala	NC(C)C(=O)	alanine
Cys	NC(CS1)C(=O)	cysteine link
Oh	O&1	hydroxy
Mphen	c1c&2cc&4cc1	1,3-substituted benzene

CHUCKLES-monomer level representation of a molecule

Monomer symbols are used in CHUCKLES in the same way as atomic symbols are used in SMILES
Ring closures are interpreted on a monomer-definition basis
The SMILES of a molecule is interpreted as if monomer symbols were replaced by their respective definitions.
If no bond is specified, monomers are joined left-to-right, bond symbols are the sames as for SMILES
"." indicates that the adjacent monomers are not bonded

EXAMPLES

AlaCys2AlaCys2

Phen23.Oh2.Oh3

Monomer Sets-

Multiple monomer choices in a given position are specified via a MonomerSet, made of semicolon-separated Monomers in brackets. The Monomer Set definition consists of its symbol, its set of Monomers and its description.

Example

Symbol Definition Description

Basepep Lys;Arg;His basic peptide residue

Thiopep Cys;Met sulfur-containing peptide residue

CHORTLES-monomer-level representation of mixtures

An extension to the CHUCKLES language that represents regular mixtures. Multiple monomer choices in a given position are specified via a MonomerSet, made of semicoln-separated Monomers in brackets.

Examples

CHORTLES	Components
Ala[Cys;Ala]Oh	2 dimers
Ala[Basepep][Thiopep][Ala;Cys]Oh	12 pentamers

CHARTS-monomer level patterns

CHARTS provides a language for monomer-level patterns specified in CHUCKLES and CHORTLES much like the SMARTS language for molecular patterns specified in SMILES.

AND syntax same as to that in CHORTLES/SMARTS and is used to specify submixtures, i.e. [A;B] means "A AND B"
OR syntax is the same as in SMARTS (comma means "or") and is used to specify components, i.e., [A,B] means "A OR B"
Pseudo monomers- Any, Begin, End
A repeat count is provided at the monomer-level, :N, :N-M,:?,:+,:*
Dot disconnections - A "." in a CHARTS indicates that the CHARTS subexpression on the left and right of the dot are to be matched independently.

Examples

CHARTS	Match found in CHORTLES
Ala[Pro;Tyr]	[Ala;Gly;Lys][Pro;Ser;Tyr][Cys;His]O
Ala[Pro,Tyr]	AlaProHisOh AlaTyrHisOh TyrAlaProHisGlyOh
Begin-Any-Any-Any-End	All Pentamers
Phe[Ala;Gly:2-]Phe	2 Phe's with 2> intervening Ala's/Gly's, e.g. PheGlyAlaPhe
Ala[Pro;Tyr]His.AlaProHis	[Ala;Gly][Pro;Ser;Tyr][Cys;His][Ala;Gly]ProHisAlaOh

Monomer Table

Summary:

CHARTS Search- Takes place at the Monomer level rather than atom-by-atom
SMARTS Search of combinatorial mixture- Atomic level searching of CHUCKLES and CHORTLES, CHUCKLES are enumerated---slow!
Submixture Search- "Find mixtures contaned by this mixture"- search target is a CHORTLES
Supermixture Search - "Find mixtures containing this mixture"

Daylight Chemical Information Systems Inc.