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 (ΔG(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, ΔG(b)(experimental) values previously reported. Therefore, the result of the multiple analysis in terms of the thermodynamic parameters, are shown as relative energy |ΔΔG| = |ΔG(b)(from) (FoldX) − ΔG(b)(experimental)|. Nine models were identified that recorded |ΔΔG| < 1.3, five models to 2.8 > |ΔΔG| > 1.3 and the other 18 models, values of |ΔΔG| > 2.8. The energetic analysis of the contribution of ΔH and ΔS to ΔG(b) to the 14-molecular model presents a ΔG(b) mostly ΔH-driven at neutral pH and at an ionic strength (I) of 0.15 M. The dependence of ΔG(b)(I,pH) at 298 K to the cruzipain−chagasin complex predicts a linear dependence of ΔG(b)(I). The computational protocol allowed the identification and prediction of thermodynamics binding energy parameters for cruzipain−chagasin-like heterodimers.