Site-specific evolutionary rates vs. flexibility and stress. Top panels: parameter-free Anisotropic Network Model (pfANM). Bottom panels: Anisotropic Network Model. Black circles: site-specific rates inferred from the sequence alignments using Rate4Site. Vertical segments: 99% confidence interval of the circles. Solid line: Stress Model predictions. Dashed line: Flexibility Model predictions. For the rate vs. flexibility plots (left panels), sites were evenly split between 20 bins according to their Mean Square Fluctuation (MSF) dynamical flexibility measure, and then MSF and evolutionary rates were averaged within bins. For the rate vs. stress plots (right panels), sites were evenly split into bins according to their Mean Local mutational Stress (MLmS), and average MLmS and rates were obtained for each bin. All variables were z-normalized for each protein.