Monomer Types, Polymer Types and Natural Analogs

Three fields classify every monomer: its polymer type, its monomer type and its natural analog. They come from HELM, the notation the service is built on, and they decide where a monomer can be used in a sequence and how tools interpret it. This article explains what each one means and how they constrain one another.

Polymer type: which kind of chain

HELM writes a macromolecule as a set of polymer chains, each of one kind, connected to each other. The polymer type of a monomer says which kind of chain it can appear in.

Polymer type	Chain	Typical monomers
`PEPTIDE`	A peptide, amide bonds along the backbone	Natural and modified amino acids, N-terminal caps such as acetyl
`RNA`	A nucleic acid, in HELM's three-part model: sugar, phosphate, base	Ribose and deoxyribose variants, phosphate and thiophosphate linkers, bases
`CHEM`	Not a chain at all: a single chemical entity attached to one or more chains	Linkers, PEG spacers, fluorescent labels, small molecules conjugated to a peptide

RNA covers DNA as well. HELM does not have a separate DNA polymer type; a deoxyribose sugar makes the chain DNA.

A symbol is unique within a polymer type. A is alanine in a peptide and adenine in a nucleic acid, and the two are different monomers that never collide. This is also why the polymer type of a monomer cannot be changed after creation: it is part of the monomer's identity.

Monomer type: which role in the chain

The monomer type says how the monomer connects to its neighbours.

Monomer type	Role	Attachment points
`Backbone`	Sits in the chain and continues it	Usually `R1` and `R2`, one towards each neighbour
`Branch`	Hangs off a backbone monomer, and ends there	Usually `R1` only, towards the backbone
`Undefined`	No chain role; used for every `CHEM` monomer	Whatever the chemistry needs

In a peptide, every amino acid is a Backbone monomer, whether natural or not. A Branch monomer in a peptide is something attached to a side chain, for example a group on the epsilon amine of a lysine. In a nucleic acid the sugars and phosphates are Backbone, and the bases are Branch: a base hangs off its sugar and does not continue the chain.

Not every combination exists. The application only offers the monomer types that are valid for the chosen polymer type:

	`PEPTIDE`	`RNA`	`CHEM`
`Backbone`	yes	yes	no
`Branch`	yes	yes	no
`Undefined`	no	no	yes

A terminal group such as an acetyl cap is not a separate type. It is registered as Backbone or Branch with a single attachment point, and the chain simply stops there.

Natural analog: which natural residue it stands in for

Most registered monomers are variants of a natural building block: a D-amino acid, an N-methylated residue, a fluorinated phenylalanine, a 2'-O-methyl ribose. The natural analog names that building block by its usual one-letter code.

Polymer type	Codes
`PEPTIDE`	The twenty amino acids `A C D E F G H I K L M N P Q R S T V W Y`, and `X` for unknown or any
`RNA`	The bases `A C G U T`, and `N` for unknown or any; `r` for a ribose-like sugar and `p` for a phosphate-like linker
`CHEM`	`-`, not applicable

The natural analog does not change the chemistry of a monomer. It is used by the tools that read sequences:

an alignment matches a modified residue to its natural counterpart, so that Nle aligns with leucine rather than being treated as a gap;
a comparison with a natural sequence, or a display in one-letter form, shows the analog;
a substitution analysis groups monomers by the residue they replace.

Choose the analog by the role the monomer plays, not only by its skeleton. Norvaline is registered as an analog of valine when it is used as an isostere of valine, and as an analog of leucine when it replaces leucine, even though its straight propyl side chain is neither. When no natural residue is a sensible match, use X for a peptide and N for a nucleic acid.

For a CHEM monomer the analog is always -. Whatever value is submitted, the service stores -, because a linker or a label is not a variant of any natural residue.

How the three fields interact

The polymer type is chosen first and filters the other two lists.
The monomer type must be valid for that polymer type, following the table above.
The natural analog must belong to that polymer type's list, and is required for PEPTIDE and RNA.

Changing the monomer type or the natural analog of an existing monomer is a material change: it creates a new version and archives the previous state. See Versioning and Deletion.