# ConforNets: Latents-Based Conformational Control in OpenFold3

arXiv: https://arxiv.org/abs/2604.18559 · HTML: https://mlsanity.com/paper/2604.18559/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 12 of its 46 references that are in the map.
- First posted on arXiv 20 Apr 2026.

## Builds on (most cited first, 12 of 12)

- [LoRA: Low-Rank Adaptation of Large Language Models](https://mlsanity.com/paper/2106.09685/) (2021)
- [Adding Conditional Control to Text-to-Image Diffusion Models](https://mlsanity.com/paper/2302.05543/) (2023)
- [Prefix-Tuning: Optimizing Continuous Prompts for Generation](https://mlsanity.com/paper/2101.00190/) (2021)
- [The Power of Scale for Parameter-Efficient Prompt Tuning](https://mlsanity.com/paper/2104.08691/) (2021)
- [Elucidating the Design Space of Diffusion-Based Generative Models](https://mlsanity.com/paper/2206.00364/) (2022)
- [Practical and Asymptotically Exact Conditional Sampling in Diffusion Models](https://mlsanity.com/paper/2306.17775/) (2023)
- [AlphaFold Meets Flow Matching for Generating Protein Ensembles](https://mlsanity.com/paper/2402.04845/) (2024)
- [Protein Conformation Generation via Force-Guided SE(3) Diffusion Models](https://mlsanity.com/paper/2403.14088/) (2024)
- [Structure Language Models for Protein Conformation Generation](https://mlsanity.com/paper/2410.18403/) (2024)
- [Unlocking hidden biomolecular conformational landscapes in diffusion models at inference time](https://mlsanity.com/paper/2512.03312/) (2025)
- [Robust Inference-Time Steering of Protein Diffusion Models via Embedding Optimization](https://mlsanity.com/paper/2602.05285/) (2026)
- [Inference-time optimization for experiment-grounded protein ensemble generation](https://mlsanity.com/paper/2602.24007/) (2026)

## Abstract (arXiv)

Models from the AlphaFold (AF) family reliably predict one dominant conformation for most well-ordered proteins but struggle to capture biologically relevant alternate states. Several efforts have focused on eliciting greater conformational variability through ad hoc inference-time perturbations of AF models or their inputs. Despite their progress, these approaches remain inefficient and fail to consistently recover major conformational modes. Here, we investigate both the optimal location and manner-of-operation for perturbing latent representations in the AF3 architecture. We distill our findings in ConforNets: channel-wise affine transforms of the pre-Pairformer pair latents. Unlike previous methods, ConforNets globally modulate AF3 representations, making them reusable across proteins. On unsupervised generation of alternate states, ConforNets achieve state-of-the-art success rates on all existing multi-state benchmarks. On the novel supervised task of conformational transfer, ConforNets trained on one source protein can induce a conserved conformational change across a protein family. Collectively, these results introduce a mechanism for conformational control in AF3-based models.