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Paper · arXiv

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

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...

AuthorsMohammed Sameer Syed, Tamara Dinneen
Primary categoryq-bio.BM
Published4 August 2026
Last updated at source4 August 2026
q-bio.BMcs.LG
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