ZetaDial: dialing net charge of protein binders at inference time for therapeutic developability

תקציר מקורי באנגליתarXiv:2609.05451v1 Announce Type: cross Abstract: Net charge is a developability-relevant property of therapeutic binders, linked to viscosity, clearance, nonspecific interaction and aggregation, and antibody screens already use charge-related criteria. Yet inverse-folding pipelines expose no way to set it to a target value. ProteinMPNN and BindCraft offer amino-acid biases, weight choices and custom losses, but neither supplies a per-protein feedback loop that measures realised charge after sampling and corrects it to a setpoint. ZetaDial contributes a post-sampling, per-protein secant controller around fixed-backbone ProteinMPNN. On matched stochastic benchmarks the secant loop reduced mean absolute error relative to a fixed-slope loop on RCSB complexes (5.17 vs 6.46 charge units) and Ca