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).
Keywords: Peptidase inhibition, structure-activity correlation, structure complementarity.
Current Enzyme Inhibition
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).
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Cite this article as:
Kipgen Lunminlal and K. Aggarwal Kamal, Shape Complementarity in Serine Protease-inhibitor Complexes Correlate to Inhibition Constants, Current Enzyme Inhibition 2014; 10 (2) . https://dx.doi.org/10.2174/1573408010666141113214226
DOI https://dx.doi.org/10.2174/1573408010666141113214226 |
Print ISSN 1573-4080 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6662 |
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