Runtimes for FreeContact. We measured the runtime (logarithmic y-axis) for different program components (x-axis) on a single thread. The program components were: “seqw” – sequence weighting; “pairfreq” – pairwise residue frequencies; “shrink” – shrinking of covariance matrix; “inv” – sparse inverse covariance estimation/covariance matrix inversion. The different colors distinguish: the original PSICOV implementation (blue), our acceleration of PSICOV (FC.psicov, yellow), our acceleration of the faster PSICOV version “sensible default” (FC.psicov-fast, green), and our implementation of EVfold-mfDCA (FC.evfold, red). The whiskers on the box plots show the most extreme data point that is less than 1.5-times the interquartile range from the box. Outliers are not shown. Total runtime of all methods tested is dominated by the sparse inverse covariance estimation/covariance matrix inversion component.