In silico analysis of homologous heterodimers of cruzipain-chagasin from structural models built by homology

The present study gives an overview of the binding energetics of the homologous heterodimers of cruzipain−chagasin based on the binding energy (∆G_b) prediction obtained with FoldX. This analysis involves a total of 70 homologous models of the cruzipain−chagasin complex which were constructed by homology from the combinatory variation of nine papain-like cysteine peptidase structures and seven cysteine protease inhibitor structures (as chagasin-like and cystatin-like inhibitors). Only 32 systems have been evaluated experimentally, ∆G_b ^experimental values previously reported. Therefore, the result of the multiple analysis in terms of the thermodynamic parameters, are shown as relative energy |∆∆G| = |∆G_b ^{from FoldX} − ∆G_b ^experimental |. Nine models were identified that recorded |∆∆G| < 1.3, five models to 2.8 > |∆∆G| > 1.3 and the other 18 models, values of |∆∆G| > 2.8. The energetic analysis of the contribution of ∆H and ∆S to ∆G_b to the 14-molecular model presents a ∆G_b mostly ∆H-driven at neutral pH and at an ionic strength (I) of 0.15 M. The dependence of ∆G_b (I,pH) at 298 K to the cruzipain−chagasin complex predicts a linear dependence of ∆G_b (I). The computational protocol allowed the identification and prediction of thermodynamics binding energy parameters for cruzipain−chagasin-like heterodimers.