ThermoMPNN-D

ThermoMPNN-D predicts protein stability changes (ΔΔG, kcal/mol) for single and double point mutations using a structure-based neural network derived from ProteinMPNN. The API exposes three modes: single-mutation, additive double-mutation (sum of two single ΔΔG values), and epistatic double-mutation prediction, with optional site-saturation mutagenesis scans when mutations are omitted. A distance filter (Å) restricts double mutations to nearby residues, and a configurable ΔΔG threshold (default ≤ -0.5 kcal/mol) prioritizes stabilizing variants for protein engineering.