Molecular docking and pharmacokinetic evaluation of natural compounds as targeted inhibitors against Crz1 protein in Rhizoctonia solani

Abstract

Crz1p regulates Calcineurin, a serine-threonine-specific protein phosphatase, in Rhizoctonia solani. It has attracted consideration as a novel target of antifungal therapy based on studies in numerous pathogenic fungi, including, Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus. To investigate whether Calcineurin can be a useful target for the treatment of Crz1 protein in R. solani causing wet root rot in Chickpea. The work presented here reports the in-silico studies of Crz1 protein against natural compounds. This study Comprises of quantitative structure-toxicity relationship (QSTR) and quantitative structure-activity relationship (QSAR). All compounds showed high binding energy for Crz1 protein through molecular docking. Further, a pharmacokinetic study revealed that these compounds had minimal side effects. Biological activity spectrum prediction of these compounds showed potential antifungal properties by showing significant interaction with Crz1. Hence, these compounds can be used for the prevention and treatment of wet root rot in Chickpea.

Keywords: Crz1; QSAR; QSTR; chickpea; pharmacokinetic.

Figure 1

(I) Three-dimensional structure of Solano Crz1 protein predicted by I-TASSER. (II) Alignment of query protein (cyan) with structural analog (light pink) 5v3jE in PDB library.

Figure 2

Validation of top score Crz1 model of I-TASSER by (A) PROCHECK Ramachandaran plot (B) Mol Probity Ramachandaran plot.

Figure 3

Binding pocket identification by CASTp server: (A) Light blue color boxes highlight the amino acid residues present in the binding site, (B) Shows the binding sites of Crz1 protein.

Figure 4

Molecular docking of compounds with Crz1: (A) Surface view of protein with compound Alpha amyrin and (B) 2D schematic diagram showing interactions of compound Alpha amyrin to the Crz1. (C) Surface view of protein with compound Fludioxonil (D) 2D schematic diagram showing interactions of compound Fludioxonil to the Crz1. Residues involved in hydrogen bonding, van der Waals interactions, carbon-hydrogen, and Pi-alkyl are represented in different color indicated in the inset.