Searching for molecular edits at inference time and distilling the search hit 2.8 times the strict-success coverage of the RL baseline
AspireAI community · arXiv (Zhang, Shekhar, McLevige & Zhang)
Refining a drug candidate means improving several properties at once without drifting away from the molecule's scaffold, and reinforcement-learning post-training does that but needs expensive task-specific data. ReMedI treats the molecular language model as a proposer inside a Metropolis-Hastings search at inference time, then distills those search traces back into the base model, which improved zero-shot generation on roughly 7.8 times less training data than the C-MORAL baseline and reached about 2.8 times its strict-success coverage across the C-MuMOInstruct and SMDD benchmarks on three backbones, including on out-of-distribution tasks at matched lead similarity. The honest limits: the comparison is against one RL baseline, strict-success coverage is a specific multi-objective metric rather than a general accuracy, and the abstract reports no absolute property values.
Read the story and explore more from the AspireAI community.
Two sparse-autoencoder analyses have resisted scaling: matching semantically similar features across layers, and compressing large feature circuits into interpretable supernodes. This paper argues both are the same underlying problem, estimating semantic distances between SAE features that sit on different activation manifolds. Its representation treats each feature not as a single decoder vector but as an activation-weighted distribution over the hidden states expressing it, projects those distributions into a shared reference space, and compares them with Wasserstein distance. The representation is proved invariant to activation rescaling and stable under perturbation, and recovers true matches under finite-sample margin conditions. Empirically it outperformed decoder-vector and LLM-based baselines and captured subtle functional distinctions between related features, and it compressed large feature circuits into interpretable supernodes automatically. The limitation is that this is interpretability tooling: the paper demonstrates better feature matching and circuit compression, not that downstream interpretability claims become more accurate.