TY - JOUR
T1 - In silico analysis of homologous heterodimers of cruzipain-chagasin from structural models built by homology
AU - Reyes-Espinosa, Francisco
AU - Juárez-Saldivar, Alfredo
AU - Palos, Isidro
AU - Herrera-Mayorga, Verónica
AU - García-Pérez, Carlos
AU - Rivera, Gildardo
N1 - Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/3/2
Y1 - 2019/3/2
N2 - The present study gives an overview of the binding energetics of the homologous heterodimers of cruzipain−chagasin based on the binding energy (∆Gb) 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, ∆Gb experimental values previously reported. Therefore, the result of the multiple analysis in terms of the thermodynamic parameters, are shown as relative energy |∆∆G| = |∆Gb from FoldX − ∆Gb 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 ∆Gb to the 14-molecular model presents a ∆Gb mostly ∆H-driven at neutral pH and at an ionic strength (I) of 0.15 M. The dependence of ∆Gb (I,pH) at 298 K to the cruzipain−chagasin complex predicts a linear dependence of ∆Gb (I). The computational protocol allowed the identification and prediction of thermodynamics binding energy parameters for cruzipain−chagasin-like heterodimers.
AB - The present study gives an overview of the binding energetics of the homologous heterodimers of cruzipain−chagasin based on the binding energy (∆Gb) 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, ∆Gb experimental values previously reported. Therefore, the result of the multiple analysis in terms of the thermodynamic parameters, are shown as relative energy |∆∆G| = |∆Gb from FoldX − ∆Gb 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 ∆Gb to the 14-molecular model presents a ∆Gb mostly ∆H-driven at neutral pH and at an ionic strength (I) of 0.15 M. The dependence of ∆Gb (I,pH) at 298 K to the cruzipain−chagasin complex predicts a linear dependence of ∆Gb (I). The computational protocol allowed the identification and prediction of thermodynamics binding energy parameters for cruzipain−chagasin-like heterodimers.
KW - Chagasin-like
KW - Cruzipain
KW - Cystatin-like
KW - Molecular modelling
KW - Trypanosoma cruzi
UR - http://www.scopus.com/inward/record.url?scp=85062980799&partnerID=8YFLogxK
U2 - 10.3390/ijms20061320
DO - 10.3390/ijms20061320
M3 - Artículo
C2 - 30875920
SN - 1661-6596
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 6
M1 - 1320
ER -