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Computational Inhibition Studies of the Human Proteasome by Argyrin‐Based Analogues with Subunit Specificity
Author(s) -
Loizidou Eriketi Z.,
ZeinalipourYazdi Constantinos D.
Publication year - 2014
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12298
Subject(s) - protein subunit , proteasome , docking (animal) , chemistry , computational biology , biochemistry , selectivity , stereochemistry , biology , gene , medicine , nursing , catalysis
A computational procedure was developed to study the subunit‐specific interactions of the proteasome inhibitors argyrin A and F, with the aim of indentifying the determinants of subunit selectivity. Three‐dimensional models of humanized proteasome active sites β 1 , β 2 and β 5 were developed and subsequently used in molecular docking simulations with the argyrin analogues. The subunit selectivity exhibited by each analogue could be explained based on the site‐specific interactions and a probability‐based specificity parameter derived in this study. A rational approach that involved maximizing site‐specific interactions was followed to guide the design of new argyrin analogues as specific inhibitors of the caspase‐like ( β 1 site) activity.