AF3 Off-target ipTM Specificity

License: This constraint can use multiple tools, each under its own license. See the Tools Used tab and each tool’s page for license details.

This constraint is open source. Any third-party models, product names, or trademarks referenced are the property of their respective owners, and Proto is not affiliated with them.

Tools Used Tools Used Source Source

evo-design/proto-language/proto_language/constraint/protein_structure/af3_offtarget_iptm_specificity_constraint.py

View source

Constraint contributors

Score AF3-based off-target specificity margin using ipTM. For each candidate tuple, builds the protein + target-DNA complex and one protein + off-target-DNA complex per off-target motif (motif substituted at dna_indices), folds them all in a single predict_structures batch, and reads iptm from each. The score is the specificity margin target_iptm - best_off_target_iptm against desired_margin: 0.0 when the margin is met or exceeded, 1.0 when there is no advantage. Supported tools: AlphaFold3 (any ipTM-producing structure tool configured via structure_tool).

API Reference

ConfigAF3OffTargetIPTMSpecificityConfig Source

Configuration for the AF3 off-target ipTM specificity constraint.

string

required

Full forward DNA scaffold (A/C/G/T) used for target folding.

string

required

Target motif in A/C/G/T placed at dna_indices in the scaffold.

List[string]

required

Off-target motifs substituted at dna_indices for AF3 specificity.

List[integer]

required

0-based indices of motif positions in target_dna_sequence.

number

default:"0.05"

Desired margin target_iptm - best_off_target_iptm.

boolean

default:"True"

Include reverse-complement DNA strand for dsDNA AF3 folding.

enum

default:"alphafold3"

Predictor for the protein-DNA complex; must be DNA-capable (alphafold3/boltz2/protenix).Options: esmfold, esmfold2, alphafold3, boltz2, chai1, protenix, alphafold2, alphafold2_binder

ESMFoldConfig

Configuration for ESMFold structure prediction.

ESMFold2Config

Configuration for ESMFold2 structure prediction.

AlphaFold3Config

Configuration for AlphaFold3 structure prediction.

Boltz2Config

Configuration for Boltz2 structure prediction.

Chai1Config

Configuration for Chai1 structure prediction.

ProtenixConfig

Configuration for Protenix structure prediction.

AlphaFold2Config

Configuration for the general AlphaFold2 multimer structure predictor.

AlphaFold2BinderStructureConfig

Configuration for the AF2 binder-design backend.

ReturnsConstraintOutput

Per-candidate specificity score in [0, 1] (lower is better) with target_iptm / best_off_target_iptm / iptm_advantage / desired_margin metadata (plus an iptm_error flag when the predictor omits iptm). The predicted target complex attaches to slot 0.

Usage

Off-target specificity for a designed DNA-binding protein with AF3:

python

>>> from proto_language.core import Segment
>>> binder = Segment(length=120, sequence_type="protein")
>>> specificity = Constraint(
...     inputs=[binder],
...     function=af3_offtarget_iptm_specificity_constraint,
...     function_config={
...         "structure_tool": "alphafold3",
...         "target_dna_sequence": "ACGTACGTACGT",
...         "target_motif": "GTAC",
...         "off_target_motifs": ["AAAA", "TTTT"],
...         "dna_indices": [2, 3, 4, 5],
...     },
... )

Metadata

Property	Value
Key	`af3-offtarget-iptm-specificity`
Function	`af3_offtarget_iptm_specificity_constraint`
Category	`protein_structure`
Mode	`discrete`
Uses GPU	`True`
Supported Types	`protein`, `dna`

Language

Language Concepts

Language Guides

Constraints

Generators

Optimizers

AF3 Off-target ipTM Specificity

API Reference

Usage

Metadata

​API Reference

​Usage

​Metadata

API Reference

Usage

Metadata