Target-conditioned binder generation
Генерация binder'а к заданному target surface / epitope.
Generative taskБиологическая и инженерная цель
Получить sequence/structure binder'а, complementary к выбранному epitope.
Возможные исходные данные
- target structure
- hotspots/epitope
- optional format constraints
Что именно генерируется
- binder sequence and/or complex geometry
Классы генераторов
- target-conditioned-binder
Какие архитектурные подходы используются
| Стратегия | Что генерирует | Представление | Примеры | Ограничение | Sampling | Novel topology | Integrated scoring | Complexity |
|---|---|---|---|---|---|---|---|---|
| Backbone diffusion + inverse folding + complex filter | Binder backbone then sequence | SE(3) frames + sequence tokens | RFdiffusion, RFantibody | Hotspot specification сильно влияет на outcome | Diffusion then MPNN | Да для miniproteins; ограничено для antibody frameworks | Complex predictor | Trajectories × MPNN samples × predictor recycles |
| Differentiable structure hallucination | Binder sequence–complex | AF2-optimized sequence/structure | BindCraft | AF2 bias; не antibody generator | Gradient-based optimization + filters | Да, в пределах AF2-designable folds | AF2 confidence + Rosetta | Optimization steps + MPNN redesign |
Architecture-to-workflow consequences
| Архитектурное решение | Практическое следствие |
|---|---|
| Target truncation | Можно потерять long-range context. |
| Integrated complex predictor | Увеличивает cost, но даёт in-loop filtering. |
Compute и deployment
- GPU-days возможны на кампанию.
- Antibody и miniprotein pipelines несопоставимы по hit rate.
Доступные инструменты
| Инструмент | Generated object | Публикация | Evidence |
|---|---|---|---|
| AlphaProteo | Binder sequences/structures | Preprint Technical report | 3–4 prospective binding/functional validation |
| BindCraft | Binder sequence and designed target–binder complex | Peer-reviewed | 3–4 prospective binding and functional validation |
| BoltzGen | Binder sequence–structure and target complex | Preprint | 3–4 prospective binding/functional validation |
| RFdiffusion | Protein backbone / complex geometry; sequence is downstream | Peer-reviewed | 3–4 prospective binding/functional/structural validation |
Типовые workflows
- Target-conditioned miniprotein binder (BindCraft)
- Target-conditioned de novo antibody (RFantibody)
- All-atom universal binder generation (BoltzGen)
Evidence summary
BindCraft/RFdiffusion — general binders; RFantibody/tFold — antibody-specific.
Что нельзя сравнивать напрямую
- General binder ≠ antibody.
- Internal interface confidence ≠ measured Kd.
Как выбирать
- Non-antibody miniprotein — BindCraft.
- VHH/scFv de novo — RFantibody.
- Universal all-atom, preprint — BoltzGen.