Dissecting mutational allosteric effects in alkaline phosphatases associated with different Hypophosphatasia phenotypes: An integrative computational investigation
Fig 7
(A) The distribution of ΔΔG and ΔBC for ALPL mutations. Scatterplot showing the distribution of ΔBC vs ΔΔG of different mutation types. Severe, mild and control mutations are depicted in red, yellow, and blue, respectively. N47I, L289F, and M355I are three severe mutations with low ΔΔG and high ΔBC. Among the three significant mutations predicted by the scatterplot, two (E452K and R391K) were not originally included in the severe mutation group but were validated as two severe mutations in the newly collected clinical samples. (B) Mean values of three replicas of the differential RMSF (ΔRMSF) of N47I (blue), L289F (red), and M355I (green) with respect to WT. For each system, a replica of 500 ns was singled out to compare the BC values of the two different networks of TNSALP WT (C) and N47I (D) mutant. The green and grey lines show the BC values of residues of DRN and AACEN. Mild and severe mutations are highlighted as yellow and red diamonds, respectively.