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Bioinformatics tools that predict protein stability changes upon point mutations have made a lot of progress in the last decades and have become accurate and fast enough to make computational mutagenesis experiments feasible, even on a proteome scale. Despite these achievements, they still suffer from important issues that must be solved to allow further improving their performances and utilizing them to deepen our insights into protein folding and stability mechanisms. One of these problems is their bias toward the learning datasets which, being dominated by destabilizing mutations, causes predictions to be better for destabilizing than for stabilizing mutations.

Quantification of biases in predictions of protein stability changes upon mutations