STRIDE: Post-Training LLMs to Reason and Refine Bio-Sequences via Edit Trajectories

Fuente: arXiv
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Auteurs principaux: Zhang, Daiheng, Zhang, Shiyang, He, Sizhuang, Zhang, Yangtian, Rizvi, Syed Asad, van Dijk, David
Format: Preprint
Publié: 2026
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author Zhang, Daiheng
Zhang, Shiyang
He, Sizhuang
Zhang, Yangtian
Rizvi, Syed Asad
van Dijk, David
author_facet Zhang, Daiheng
Zhang, Shiyang
He, Sizhuang
Zhang, Yangtian
Rizvi, Syed Asad
van Dijk, David
contents Discrete biological sequence optimization requires iterative refinement under strict syntactic constraints. Diffusion models offer progressive refinement but do not naturally expose controllable discrete edit operations, while autoregressive LLMs often lack explicit long-horizon planning for constrained edits. We propose STRIDE (Sequence Trajectory Refinement via Internalized Denoising Emulation), a post-training framework that trains an LLM to emit executable trajectories of atomic edits (INSERT/DELETE/REPLACE) as a verifiable reasoning trace for variable-length refinement. STRIDE combines supervised fine-tuning on Levenshtein-aligned shortest edit demonstrations with group-based policy optimization to align edit trajectories with task rewards while preserving coherent editing behavior. Across protein fluorescence and instruction-conditioned molecular optimization, STRIDE improves variable-length protein editing success from 42% to 89% while increasing novelty from 47% to 97%, and yields stronger validity and controllability compared to diverse baselines. The code is published at https://github.com/daiheng-zhang/STRIDE.
format Preprint
id arxiv_https___arxiv_org_abs_2603_03573
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle STRIDE: Post-Training LLMs to Reason and Refine Bio-Sequences via Edit Trajectories
Zhang, Daiheng
Zhang, Shiyang
He, Sizhuang
Zhang, Yangtian
Rizvi, Syed Asad
van Dijk, David
Computational Engineering, Finance, and Science
Discrete biological sequence optimization requires iterative refinement under strict syntactic constraints. Diffusion models offer progressive refinement but do not naturally expose controllable discrete edit operations, while autoregressive LLMs often lack explicit long-horizon planning for constrained edits. We propose STRIDE (Sequence Trajectory Refinement via Internalized Denoising Emulation), a post-training framework that trains an LLM to emit executable trajectories of atomic edits (INSERT/DELETE/REPLACE) as a verifiable reasoning trace for variable-length refinement. STRIDE combines supervised fine-tuning on Levenshtein-aligned shortest edit demonstrations with group-based policy optimization to align edit trajectories with task rewards while preserving coherent editing behavior. Across protein fluorescence and instruction-conditioned molecular optimization, STRIDE improves variable-length protein editing success from 42% to 89% while increasing novelty from 47% to 97%, and yields stronger validity and controllability compared to diverse baselines. The code is published at https://github.com/daiheng-zhang/STRIDE.
title STRIDE: Post-Training LLMs to Reason and Refine Bio-Sequences via Edit Trajectories
topic Computational Engineering, Finance, and Science
url https://arxiv.org/abs/2603.03573