Using Sequence Alignments to Predict Protein Structure and Stability With High Accuracy

Abstract

We present a sequence-based probabilistic formalism that directly addresses co-operative effects in networks of interacting positions in proteins, providing significantly improved contact prediction, as well as accurate quantitative prediction of free energy changes due to non-additive effects of multiple mutations. In addition to these practical considerations, the agreement of our sequence-based calculations with experimental data for both structure and stability demonstrates a strong relation between the statistical distribution of protein sequences produced by natural evolutionary processes, and the thermodynamic stability of the structures to which these sequences fold.