Relational dynamics obtained through simulation studies of thioredoxin reductase: From a multi-drug resistant Entamoeba histolytica

Microbial enteric infections cause diarrhea, dysentery, and fever that constitute huge health problems worldwide. Entamoeba histolytica is amulti-drug resistant bacterial pathogen involves in instigating enteric infections. Multi-drug resistant E. histolytica is responsible for higher rate of mortality and morbidity. In the present study, a systematic in-silico pipeline applied to screen potential drug targets that are considered essential for pathogen survival. Thioredoxin reductase (TrxR) enzyme is concluded as a potential drug target bearing features of drug-ability, three-dimensional structure availability, favorable physiochemical properties, involvement in core pathways, rich interactome and broad-spectrumconservation. A library of antibacterial compounds was virtually screened against TrxR via molecular docking. The best docked complexes subjected to molecular dynamics simulation to observe dynamic behavior of complex. Root mean square deviation deduced interconversions helix-coil-helix-coil, and beta-turn-beta in TrxR and are highly flexible. Transitional changes observed in protein as a result of relational dynamics have a significant influence on the binding mechanism of inhibitor with in the protein cavity. Other factors: root mean square fluctuation, beta-factor and radius of gyration values show coherence with root mean square deviation results. Furthermore, crucial hydrogen bonds of residues Glu33 and Ala115 with inhibitor revealed through hydrogen bond analysis. Axial frequency distribution revealed residues Glu33 and Ala115 atoms showing high affinity for inhibitor though a minor tilting behavior was observed. Poisson Boltzmann or Generalized Born Surface Area Continuum Solvation (MM (PB/GB) SA) methods indicate van der Waal interactions as dominant interactions. These analyses revealed (1-(carboxymethyl)-4-(4-methylthiazole-5-carboxamido)-3H-pyrazol-1-ium-3-ide) as the potential lead compound. This study will facilitate researchers to discover and develop more effective leads compounds against E. histolytica. (C) 2020 Elsevier B.V. All rights reserved.yy