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