Protein Stability is Determined by Single-Site Bias Rather Than Pairwise Covariance
Sequence biases at individual positions can be used to design more stable protein variants, while correlation between pairs of residues has also been shown to be important for specifying protein structure and function.
The Potts model has been utilized in recent studies to separate the contributions of single-site biases and pair correlations on protein stability and function. This approach allows researchers to identify sequence biases that provide information related to protein structure, stability, and function. By applying a Potts model to design groups of protein sequences with varying levels of single-site biases and pair correlations, it has been demonstrated that these models can improve predictions of protein fitness, activity, and stability compared to simpler models.