Protein stability predictors no longer contradict themselves: EvoPhi-DDG turns an alignment model into a potential, so forward and reverse scores cancel exactly
Protein stability-change predictors often disagree with themselves: swapping the two sequences does not flip the sign of the prediction, and paths that detour through intermediate states at the same site fail to close. Without retraining, EvoPhi-DDG rewrites the family-alignment predictor MSAesm_ddG as a difference of an effective potential conditioned on the mutation site and alignment context, giving exact sign reversal and exact same-site additivity under a fixed alignment context. Averaged with equal weights with the published JanusDDG, it reaches a Pearson correlation of 0.59 on S669, against 0.55 for JanusDDG and 0.53 for EvoPhi-DDG.