In silico structural characterization of protein targets for drug development against Trypanosoma cruzi

Trypanosoma cruzi is the protozoan pathogen responsible for Chagas disease, which is a major public health problem in tropical and subtropical regions of developing countries and particularly in Brazil. Despite many studies, there is no efficient treatment against Chagas disease, and the search for...

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Bibliographic Details
Published in:Journal of molecular modeling 2016-10, Vol.22 (10), p.244-14, Article 244
Main Authors: Lima, Carlyle Ribeiro, Carels, Nicolas, Guimaraes, Ana Carolina Ramos, Tufféry, Pierre, Derreumaux, Philippe
Format: Article
Language:English
Subjects:
Aqueous solutions
Biochemistry, Molecular Biology
Biophysics
Chagas disease
Characterization and Evaluation of Materials
Chemistry
Chemistry and Materials Science
Computer Appl. in Life Sciences
Computer Applications in Chemistry
Cysteine
Developing countries
Drug development
Dynamic structural analysis
LDCs
Life Sciences
Molecular dynamics
Molecular Medicine
Original Paper
Proteins
Protozoa
Public health
Reductases
Theoretical and Computational Chemistry
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Summary:Trypanosoma cruzi is the protozoan pathogen responsible for Chagas disease, which is a major public health problem in tropical and subtropical regions of developing countries and particularly in Brazil. Despite many studies, there is no efficient treatment against Chagas disease, and the search for new therapeutic targets specific to T. cruzi is critical for drug development. Here, we have revisited 41 protein sequences proposed by the analogous enzyme pipeline, and found that it is possible to provide structures for T. cruzi sequences with clear homologs or analogs in H. sapiens and likely associated with trypanothione reductase, cysteine synthase, and ATPase functions, and structures for sequences specific to T. cruzi and absent in H. sapiens associated with 2,4-dienoyl-CoA reductase, and leishmanolysin activities. The implications of our structures refined by atomistic molecular dynamics (monomer or dimer states) in their in vitro environments (aqueous solution or membrane bilayers) are discussed for drug development and suggest that all protein targets, except cysteine synthase, merit further investigation.
ISSN:1610-2940
0948-5023
DOI:10.1007/s00894-016-3115-9