TopoCompile: Molecular Generation with Exact Global Count Constraints

Overview & Synopsis

Molecular generation designs novel molecules with desired structures and properties. Global count constraints specify molecular size, elemental composition, and ring content without prescribing detailed structure. Property-conditioned generators steer generation toward such targets but do not guarantee exact satisfaction. We introduce TopoCompile, which combines an autoregressive component-tree generator with a dynamic-programming compiler for supported component-additive integer counts. TopoCompile represents molecules as trees of intact ring systems and individual atoms, making each supported count additive over components. At each step, an autoregressive Transformer scores component and attachment actions, while the compiler masks actions with no target-satisfying completion. Within the fixed component vocabulary and typed attachment rules, constrained decoding guarantees exact equality for supported non-negative, component-additive integer counts. Applied at inference time, these checks let the same trained generator support different targets and count combinations without retraining. Across four benchmarks, TopoCompile achieves 100% Exact-valid yield for Common and Rare four-count target groups; the strongest baseline within each dataset reaches 44.9% or less on Rare targets. In unconditional generation, it achieves the highest validity or valid-unique-novel (V.U.N.) among the compared methods across all four benchmark datasets.