DiMOS: Doob-Guided Inference-Time Multi-Objective Search for Scientific Design

Ziqing Wang, Qijie Zhu, Weimin Wu, Zeqi Ye, Minshuo Chen +2

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…