Molecular Modeling of Renin Inhibitor P2 Substituents
In the absence of an accurate three-dimensional structure of human renin, the crystal structures of fungal enzymes have provided reasonable templates for the elaboration of a renin model.1 In addition, the increasing number of bound inhibitor structures determined from co-crystallizations with endothiapepsin,2 have considerably enhanced our understanding of the multiple binding modes available to the side chains. These experimental data have formed the bases for molecular modeling studies3 applied to a limited series of highly flexible thiourea P2 side chains. The results provide evidence for an inter-sidechain dependency that will ultimately govern the particular binding affinity. These findings are in agreement with an independent study recently reported in the literature.4
KeywordsMolecular Modeling Renin Inhibitor Molecular Modeling Studies3 Limited Series Strong Binding Affinity
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