In silico Phylogenetics and Molecular Docking Studies of Rhodanese from Yeast (Saccharomyces cerevisiae)

Abstract

In silico Phylogenetics and Molecular Docking Studies of Rhodanese from Yeast (Saccharomyces cerevisiae) Aim: To evaluate the in silico phylogenetics, binding energy and poses of rhodanese from Yeast (Saccharomyces cerevisiae) with known substrates and inhibitors. Study Design: The three categories of ligands which include substrates, salts and effectors, were used against the phylogenetically conserved rhodanese from yeast. Place and Duration of Study: The study was carried out at the Enzyme Biotechnology and Bioinformatics Unit, Department of Biochemistry, Federal University of Technology Akure, Nigeria. The research was carried out from January to March 2018. Methodology: The properties of rhodanese from S. cerevisiae was evaluated using EMBOSS server, phylogeny was constructed through Blastp and ClustalO server, and molecular docking was carried out using AutoDock Tools and AutoDock Vina software. Results: Evolutionary divergence was observed for two rhodanese (RDL1 and RDL2) from two gene loci of yeast, with different active site amino acid residues that showed deletion of ten amino acids residues during paralogue event, and optimum pH of 5 and 9 respectively.RDL2 was further analyzed based on the sequence length, phylogeny and the characteristic of the active site similar to previous experimental reports on rhodaneses. The binding energy obtained from molecular docking were -3.0, -5.2, -5.7, -4.2, -2.5, and -1.1 kcal/mol for thiosulphate, sodium metabisulphite, EDTA, ascorbic acid, MgCl2 and ammonium persulphate respectively. However, it was observed that yeast rhodanese (RDL2) has three other binding domains apart from its active site, that functions in pre-catalysis, ionic sensitivity and acid-base sensitivity for other sulphur-containing substrates, salts and other agents respectively. Conclusion: This study provides an insight to the mechanism of rhodanese by showing the presence of a critical catalytic cysteine residue and the relationship that possibly exists between the catalytic site and other allosteric sites, and that pre-catalysis occur for sulphur-containing substrates.