DiMOS: Doob-Guided Inference-Time Multi-Objective Search for Scientific Design
Ziqing Wang, Qijie Zhu, Weimin Wu, Zeqi Ye, Minshuo Chen, Han Liu, Kaize Ding
Abstract
Scientific design often requires jointly satisfying multiple objectives and constraints. Pretrained masked diffusion models provide a generative foundation for this task, but fine-tuning them to meet these objectives and constraints incurs additional training costs, motivating inference-time guidance with frozen models. However, such guidance faces two challenges: pass-or-fail constraints and black-box reward models may provide no useful gradients, while jointly satisfying multiple requirements can leave a small feasible region, making feasible designs difficult to find within a limited inference budget. To address these challenges, we introduce DiMOS, a training-free framework for multi-objective scientific design. Using joint rewards from candidate completions, DiMOS performs approximate Doob-guided local resampling without requiring reward gradients. To allocate computation efficiently, it uses budget-efficient trajectory search to focus computation on promising continuations. Across six DNA, protein, and RNA tasks, DiMOS attains the highest joint success rate at comparable generation times, up to $1.98\times$ the strongest baseline on DNA and protein, while maintaining high sequence uniqueness and naturalness.