Title:Shape Complementarity in Serine Protease-inhibitor Complexes Correlate to Inhibition Constants
Volume: 10
Issue: 2
Author(s): Lunminlal Kipgen and Kamal K. Aggarwal
Affiliation:
Keywords:
Peptidase inhibition, structure-activity correlation, structure complementarity.
Abstract: Natural proteinaceous protease inhibitors inhibit through nonproductive binding to proteases and steric
blockage of active sites. These complexes are among the most structurally complementary protein-protein interactions. To
see if complementarity is correlated to activity, we scored the shape complementarity in 15 serine protease-inhibitor complexes
through in silico docking and compared the scores against their reported inhibition constants (Ki). A statistically
significant, moderate and positive correlation was observed between shape complementarity and Ki (R = 0.58; P = 0.023).
We also analyzed other physicochemical factors involved in serine protease-inhibitor interactions for correlation, but no
other factor was correlated to Ki. However, significant correlations were observed between hydrogen bonds and interface
areas (R = 0.762; P = 0.0004); and between hydrophobic interactions and free energies of solvation (R = -0.634;
P = 0.011).
