Modifying DNA Structures¶

MDNA supports three types of modifications on existing DNA structures: mutation, methylation, and Hoogsteen flipping. All modifications update the Nucleic object in-place.

Mutations¶

Replace nucleobases at specific positions using a dictionary of {index: new_base}:

import mdna

dna = mdna.make(sequence='AGCGATATAGA')

# Mutate position 0 → G, position 10 → C
dna.mutate({0: 'G', dna.n_bp - 1: 'C'})

dna.describe()

Complementary Strand¶

By default, the complementary strand is updated automatically (complementary=True). To mutate only the leading strand:

dna.mutate({0: 'G'}, complementary=False)

Supported Bases¶

MDNA supports canonical and non-canonical nucleobases:

Code	Name	Pairs With	Category
A	Adenine	T	Canonical
T	Thymine	A	Canonical
G	Guanine	C	Canonical
C	Cytosine	G	Canonical
U	Uracil	A	RNA incorporation
E	2-Aminopurine (2AP)	T	Fluorescent
D	tC (tricyclic cytosine)	G	Fluorescent
L	d5SICS	M	Hydrophobic UBP
M	dNaM	L	Hydrophobic UBP
B	A-analogue	S	Hachimoji
S	T-analogue	B	Hachimoji
Z	G-analogue	P	Hachimoji
P	C-analogue	Z	Hachimoji

For more details on non-canonical bases, see Non-Canonical Bases.

Note

Mutation clears cached frames, rigid parameters, and minimizer state. Call get_frames() or get_traj() after mutating to regenerate them.

Methylation¶

Add methyl groups to cytosine (C5 position) or guanine (O6 position):

dna = mdna.make(sequence='GCGCGCGAGCGA')

# Methylate specific residue indices
dna.methylate(methylations=[0, 2, 4])

CpG Methylation¶

Automatically methylate all cytosines in CpG context:

dna.methylate(CpG=True, leading_strand=0)

Warning

Only C and G residues can be methylated. Attempting to methylate A or T will be silently skipped with a warning message.

Hoogsteen Flipping¶

Rotate nucleobases around the glycosidic bond to switch between Watson-Crick and Hoogsteen base pairing:

dna = mdna.make(sequence='GCAAAGC')

# Flip base pairs 3 and 4 by 180 degrees (Hoogsteen)
dna.flip(fliplist=[3, 4], deg=180)

The deg parameter controls the rotation angle. A 180° flip produces the canonical Hoogsteen configuration.

Chaining Modifications¶

Modifications can be applied sequentially:

dna = mdna.make(sequence='GCGCAATTGCGC')

# 1. Mutate
dna.mutate({0: 'A', 11: 'T'})

# 2. Methylate CpG sites
dna.methylate(CpG=True, leading_strand=0)

# 3. Flip a base pair
dna.flip(fliplist=[5], deg=180)

# 4. Export the modified structure
dna.save_pdb('modified_dna.pdb')

Summary¶

Modification	Method	Key Arguments
Base substitution	`nucleic.mutate()`	`mutations` dict, `complementary`
Methylation	`nucleic.methylate()`	`methylations` list or `CpG=True`
Hoogsteen flip	`nucleic.flip()`	`fliplist`, `deg`