Quantitative profiling of protease specificity
Fig 3
Divergence between probability distributions of tetramer clusters in substrate selections and the naïve library is a measure of substrate specificity.
A. Distributions of relative abundances of tetramer clusters in the MMP substrate selections are significantly different from that in the naïve phage display library. Tetramer clusters within evenly spaced ranges of probabilities were binned together and their relative abundances were plotted as a function of log10 of average probabilities in the respective sets. B. A subset of tetramer clusters in substrate selections with positive cumulative contribution to K-L divergence relative to the naïve library constitutes the selectome of a protease. Cumulative contribution of individual tetramer clusters with RP values between of 0 and 4.5 for MMP-2 and 0 and 4.7 for MMP-9 to the K-L divergence relative to the naïve library is equal to 0. The K-L divergence between the probability distributions in the substrate sets of a protease with no definable specificity and the naïve library is always equal to 0. Therefore, the substrate sets with overall positive cumulative individual contributions to K-L divergences constitute the selectomes of proteases with definable specificities (MMP-2 and 9, red arrows).