Your first peptide¶

By the end of this page you will have built a cyclic peptide from a sequence string, read the HELM back, inspected its crosslinks, used a non-natural monomer, and computed its mass.

It takes about ten minutes, and assumes you have been through Your first oligonucleotide or are comfortable with the idea that HELMshaker needs a monomer library.

The mass step needs the chem extra:

pip install "helmshaker[chem]"

Step 1: load a library¶

In [1]:

from helmshaker import Molecule, MonomerLibrary

library = MonomerLibrary()
library.load_from_file("../examples/docs_library.json")

print(f"{len(library)} monomers available")

from helmshaker import Molecule, MonomerLibrary library = MonomerLibrary() library.load_from_file("../examples/docs_library.json") print(f"{len(library)} monomers available")

40 monomers available

Step 2: build a peptide from a sequence¶

You do not have to write HELM by hand. from_peptide_sequence takes a sequence string and works out the HELM, resolving connection points against the library.

In [2]:

linear = Molecule.from_peptide_sequence("CAAAC", monomer_library=library)

print(linear.to_helm())

linear = Molecule.from_peptide_sequence("CAAAC", monomer_library=library) print(linear.to_helm())

PEPTIDE1{C.A.A.A.C}$$$$V2.0

Step 3: add a disulfide¶

A crosslink is written MONOMER:POSITION-MONOMER:POSITION. Positions are 1-based. Naming the monomer as well as the position means a typo fails loudly instead of bridging the wrong pair.

In [3]:

cyclic = Molecule.from_peptide_sequence(
    "CAAAC", crosslinks="C:1-C:5", monomer_library=library
)

print(cyclic.to_helm())

cyclic = Molecule.from_peptide_sequence( "CAAAC", crosslinks="C:1-C:5", monomer_library=library ) print(cyclic.to_helm())

PEPTIDE1{C.A.A.A.C}$PEPTIDE1,PEPTIDE1,1:R3-5:R3$$$V2.0

The extra section after the first $ is the connection: residue 1 R3 to residue 5 R3, which is the disulfide.

Step 4: inspect it¶

In [4]:

data = cyclic.data

print("peptides        :", data.get_peptide_ids())
print("sequence        :", data.get_sequence("PEPTIDE1"))
print("natural analog  :", data.get_natural_sequence("PEPTIDE1"))
print("is cyclic       :", data.is_cyclic("PEPTIDE1"))

data = cyclic.data print("peptides :", data.get_peptide_ids()) print("sequence :", data.get_sequence("PEPTIDE1")) print("natural analog :", data.get_natural_sequence("PEPTIDE1")) print("is cyclic :", data.is_cyclic("PEPTIDE1"))

peptides        : ['PEPTIDE1']
sequence        : ['C', 'A', 'A', 'A', 'C']
natural analog  : CAAAC
is cyclic       : True

In [5]:

for link in data.get_crosslinks("PEPTIDE1"):
    print(f"  {link.monomer1.id}:{link.attachment1} - {link.monomer2.id}:{link.attachment2}")

for link in data.get_crosslinks("PEPTIDE1"): print(f" {link.monomer1.id}:{link.attachment1} - {link.monomer2.id}:{link.attachment2}")

  C:R3 - C:R3

Step 5: use a non-natural monomer¶

Two spellings reach the same HELM. Dot-delimited lets you name a monomer inline:

In [6]:

print(Molecule.from_peptide_sequence("C.A.Nle.R.N", monomer_library=library).to_helm())

print(Molecule.from_peptide_sequence("C.A.Nle.R.N", monomer_library=library).to_helm())

PEPTIDE1{C.A.[Nle].R.N}$$$$V2.0

Or write X as a placeholder and resolve it with a modifier, which reads better for a long sequence with one substitution:

In [7]:

print(Molecule.from_peptide_sequence("CAXRN", modifiers="X3=Nle", monomer_library=library).to_helm())

print(Molecule.from_peptide_sequence("CAXRN", modifiers="X3=Nle", monomer_library=library).to_helm())

PEPTIDE1{C.A.[Nle].R.N}$$$$V2.0

Nle has to exist in the library you pass. If it does not, the grammar cannot find its connection points and the call fails rather than inventing them.

Step 6: read a HELM back¶

Parsing HELM works the same way for peptides as for oligonucleotides:

In [8]:

capped = Molecule.from_helm("PEPTIDE1{G.A.C.[Nle].[am]}$$$$V2.0", monomer_library=library)

print(capped.data.get_sequence("PEPTIDE1"))
print(capped.data.get_natural_sequence("PEPTIDE1"))

capped = Molecule.from_helm("PEPTIDE1{G.A.C.[Nle].[am]}$$$$V2.0", monomer_library=library) print(capped.data.get_sequence("PEPTIDE1")) print(capped.data.get_natural_sequence("PEPTIDE1"))

['G', 'A', 'C', 'Nle', 'am']
GACLX

The natural-analog sequence maps Nle to L, its closest proteinogenic neighbour, and the C-terminal amide cap to X, because no amino acid corresponds to it.

Step 7: compute the mass¶

This assembles the whole structure from the monomer records, so it needs RDKit and a library whose records carry SMILES.

In [9]:

print("weight :", round(cyclic.molecular_weight(), 3))
print("formula:", cyclic.molecular_formula())

print("weight :", round(cyclic.molecular_weight(), 3)) print("formula:", cyclic.molecular_formula())

weight : 435.528
formula: C15H25N5O6S2

The disulfide is accounted for: the cyclic form is two hydrogens lighter than the linear one.

In [10]:

print("linear :", round(linear.molecular_weight(), 3), linear.molecular_formula())
print("cyclic :", round(cyclic.molecular_weight(), 3), cyclic.molecular_formula())

print("linear :", round(linear.molecular_weight(), 3), linear.molecular_formula()) print("cyclic :", round(cyclic.molecular_weight(), 3), cyclic.molecular_formula())

linear : 437.544 C15H27N5O6S2
cyclic : 435.528 C15H25N5O6S2

What next¶

• Peptide sequence grammar documents the full syntax
• Load a monomer library pulls a real peptide dictionary from TMR
• Compute mass and structure goes further into structure output