In Silico Analysis of Homologous Heterodimers of Cruzipain-Chagasin from Structural Models Built by Homology.

TitleIn Silico Analysis of Homologous Heterodimers of Cruzipain-Chagasin from Structural Models Built by Homology.
Publication TypeJournal Article
Year of Publication2019
AuthorsReyes-Espinosa F, Juárez-Saldivar A, Palos I, Herrera-Mayorga V, García-Pérez C, Rivera G
JournalInt J Mol Sci
Volume20
Issue6
Date Published2019 Mar 15
ISSN1422-0067
KeywordsAmino Acid Sequence, Binding Sites, Computer Simulation, Cysteine Endopeptidases, Humans, Models, Molecular, Multiprotein Complexes, Protein Binding, Protein Conformation, Protozoan Proteins, Structural Homology, Protein, Trypanosoma cruzi
Abstract

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.

DOI10.3390/ijms20061320
Alternate JournalInt J Mol Sci
PubMed ID30875920
PubMed Central IDPMC6470822