Not all biological molecules are fully defined, so HELM includes the ability to define ambiguous bonds.
Ambiguous bonds are defined in the second section of the HELM string. For example:
The editor shows the bond from MCC connected to a box around the peptide, indicating that there is a bond, but we do not know which monomer is connected.
There is a lot of flexibility in this approach. You can define the connection monomer by
- A number in the chain – this means only one monomer is connected
- A monomer ID – the connection could be to any monomer with that ID. This is useful when you know that the connection is to a Cys, for example, but not which Cys.
- ? – the connection could be to any monomer in the group or polymer
You can define the position of the connection:
- R group number – this is a specific connection.
- ? – the connection point on the monomer is not specified.
There are some options that are not permitted.
You can’t connect to a specific R group number when the monomer is ambiguous. Ambiguous monomers don’t have numbered R groups, they have the ability to connect to other monomers an unspecified and unlimited number of times.
Defining the monomer position when using ambiguous monomers is quite convoluted. Since the * ambiguous monomer can denote more than one monomer, it quickly becomes meaningless. Technically it is allowed, but it is best avoided.
There are other situations that are obviously not allowed:
- Numbered locations that don’t exist in the monomer chain i.e. where the location number is greater than the length of the chain.
- R groups where the number has already been used.
- R groups whose number is greater than those defined in the monomer structure.