arXiv:2605.10035cs.AI2026-05被引 1

提出可迭代优化分子的离散编辑框架,减少对人工评估依赖。

From Single-Step Edit Response to Multi-Step Molecular Optimization

论文配图:From Single-Step Edit Response to Multi-Step Molecular Optimization
图 1 · 摘自论文原文
  • 用响应预测模型学习单步编辑方向,指导每一步可行修改选择。
  • 通过弱相关分子对分解结构差异,实现过程级监督与可迁移编辑单元。
  • 构建定向编辑评分器,显著降低决策时对外部评估器的依赖。

条件分子优化旨在通过编辑分子实现特定性质变化。现实中结构相似分子数据稀少,而决策本质是局部操作:每步需从符合化学规则的候选集中选出一个局部修改。这种监督与决策层级不匹配导致基于人工评估的搜索不稳定。通过回归分子对之间的性质差异提升数据效率,但依赖人工评估循环,难以分离转化效应与全局上下文,对下一步可行编辑的选择引导有限。为此,我们提出响应导向的离散编辑优化方法(SMER-Opt),包含两个紧密耦合组件:单步分子编辑响应预测器(SMER)和基于引导树搜索的多步规划器。该方法学习编辑动作的方向性评估模型,支持约束感知规划。通过挖掘弱相关分子对,将其结构差异分解为最小编辑单元,将终点性质标注转化为过程级监督,生成可复用、可迁移的动作基元。进一步引入方向性编辑评估器,根据候选编辑使分子向目标性质变化的可能性进行打分,大幅减少决策时对外部评估器的查询需求。代码已公开于 https://anonymous.4open.science/r/SMER。

原文摘要 · Abstract (English)

Conditional molecular optimization aims to edit a molecule to realize a specified property shift. In practice, structurally similar molecule data is scarce, while decisions are inherently action-level: at each step, the system must select one local structural edit from a candidate set that is strictly filtered by chemical feasibility rules. This level mismatch between supervision and decision makes oracle-in-the-loop search unstable in molecular optimization. Regressing on property differences between molecule pairs improves data efficiency but relies on oracle-in-the-loop search, entangling transformation effects with global context and providing limited guidance for selecting the next feasible edit, often resorting to oracle-in-the-loop search. For this reason, we propose a response-oriented discrete edit optimization approach comprising two tightly coupled components: a single-step molecular edit response predictor (SMER) and a multi-step planner that composes local predictions into optimization trajectories via guided tree search (SMER-Opt). The approach learns a directional evaluation model over edit actions to support constraint-aware planning. It mines weakly related molecule pairs and decomposes their structural differences into minimal edit units, turning endpoint property annotations into process-level supervision and yielding reusable, transferable action primitives. A directional edit evaluator then scores feasible candidate edits by their likelihood of moving the molecule toward the desired property change, substantially reducing dependence on external evaluator queries at decision time. Code is available at https://anonymous.4open.science/r/SMER.

分子优化离散优化生成模型化学信息学

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