# Chamaileon: Cross-Context Binder Design with Contextualized Modeling and Mixed Sampling

arXiv: https://arxiv.org/abs/2607.23518 · HTML: https://mlsanity.com/paper/2607.23518/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 16 of its 42 references that are in the map.
- First posted on arXiv 26 Jul 2026.

## Builds on (most cited first, 16 of 16)

- [Score-Based Generative Modeling through Stochastic Differential Equations](https://mlsanity.com/paper/2011.13456/) (2020)
- [Generative Flows on Discrete State-Spaces: Enabling Multimodal Flows with Applications to Protein Co-Design](https://mlsanity.com/paper/2402.04997/) (2024)
- [A General Framework for Inference-time Scaling and Steering of Diffusion Models](https://mlsanity.com/paper/2501.06848/) (2025)
- [Less-to-More Generalization: Unlocking More Controllability by In-Context Generation](https://mlsanity.com/paper/2504.02160/) (2025)
- [Reward Forcing: Efficient Streaming Video Generation with Rewarded Distribution Matching Distillation](https://mlsanity.com/paper/2512.04678/) (2025)
- [Proteina: Scaling Flow-based Protein Structure Generative Models](https://mlsanity.com/paper/2503.00710/) (2025)
- [InPO: Inversion Preference Optimization with Reparametrized DDIM for Efficient Diffusion Model Alignment](https://mlsanity.com/paper/2503.18454/) (2025)
- [Scaling Atomistic Protein Binder Design with Generative Pretraining and Test-Time Compute](https://mlsanity.com/paper/2603.27950/) (2026)
- [Smoothed Preference Optimization via ReNoise Inversion for Aligning Diffusion Models with Varied Human Preferences](https://mlsanity.com/paper/2506.02698/) (2025)
- [OmniTry: Virtual Try-On Anything without Masks](https://mlsanity.com/paper/2508.13632/) (2025)
- [An All-Atom Generative Model for Designing Protein Complexes](https://mlsanity.com/paper/2504.13075/) (2025)
- [Dimension-Reduction Attack! Video Generative Models are Experts on Controllable Image Synthesis](https://mlsanity.com/paper/2505.23325/) (2025)
- [Generative artificial intelligence for de novo protein design](https://mlsanity.com/paper/2310.09685/) (2023)
- [Multi-state Protein Design with DynamicMPNN](https://mlsanity.com/paper/2507.21938/) (2025)
- [DMGD: Train-Free Dataset Distillation with Semantic-Distribution Matching in Diffusion Models](https://mlsanity.com/paper/2605.03877/) (2026)
- [Offline Preference Optimization for Rectified Flow with Noise-Tracked Pairs](https://mlsanity.com/paper/2605.09433/) (2026)

## Abstract (arXiv)

The rapid evolution of generative models has unlocked new potentials in protein binder design, a pivotal task in structural biology, by facilitating end-to-end generation via joint sequence-structure modeling or hallucination. However, existing approaches are predominantly implemented under a single-target, single-state assumption, limiting their ability to model multi-target or multi-state interactions required for advanced function-oriented protein design. Here, we introduce Chamaileon, which unifies multi-target and multi-state binder design by formulating the problem as cross-context binding landscape modeling. The framework is underpinned by a training paradigm termed In-Context Complex Co-Design (I3CD) for context-aware sequence-structure co-modeling. During inference, we employ Mixture-of-Paths Sampling (MoPS), a scalable strategy that optimizes a single sequence across contexts while alleviating the scarcity of high-quality multi-conformational paired data. Extensive evaluation on our newly constructed benchmark, CROSS, demonstrates that Chamaileon effectively generates sequences adaptable to diverse conformational landscapes and multi-target requirements. The code is available on https://github.com/caohengyuan/Chamaileon.