An alternative way to look at sequence alignment within the context of a crystal structure is to simply align MMP7 to either MMP12 or MMP3 . Above (Fig. 6) are surface structures of mmp 3, 7, and 12 . In the case of MMPs, changes in surface amino acids seem to be the primary effectors of active site structure. Aligning MMP12 to MMP3 in pymol suggest residues H172Y, G179N, T180I, A186G,  T210I, F202R, and G209C contribute heavily to the differences in active site structure. Sites 172, 179, and 180 were identified in the python distance alignment while 186, 202, 209 and 210 are all greater than 18A from the active site zinc. Aligning MMP3 and MMP7 suggest R101S, T102L, L179N, Q202R, T208L, T210I, A230T, and L240T strongly contribute to active site differences between MMP3 and MMP7. Residues 101, 102 and 179 were identified in both the python distance alignment and the PyMol alignment while residues 202, 208, 210, 230, and 240 were greater than 17A from the active site. 


The next step is to model elastin and IgG into the active sites of MMP3, 7, and 12. Using residues identified with the python based pairwise alignment and PyMol's alignment tool I will model site directed mutagenesis experiments in silico to for further evidence mutations to increase the free energy of IgG degradation in MMP7 or decrease free energy of MMP12 elastinase activity. 



Fig. 6. Structures of MMP3 (top), MMP7 (middle), and MMP12 (bottom). Alignment shows several residues in the active site cleft that at greater than 20A away that may sterically and/or electrostatically affect elastin and IgG binding. Yellow residues can participate in H-bonding, red residues are charged, and blue residues are hydrophobic.