title: Molecular docking of glucosamine-6-phosphate synthase in Rhizopus oryzae.
abstract: Recent expansion of immunocompromised population has led to significant rise in zygomycosis caused by filamentous fungus Rhizopus oryzae. Due to emergence of fungal resistance and side-effects of antifungal drugs, there is increased demand for novel drug targets. The current study elucidates molecular interactions of peptide drugs with G-6-P synthase (catalyzing the rate-limiting step of fungal cell wall biosynthetic pathway) of R.oryzae by molecular docking studies. The PDB structures of enzyme in R.oryzae are not known which were predicted using I-TASSER server and validated with PROCHECK. Peptide inhibitors, FMDP and ADGP previously used against enzyme of E.coli (PDBid: 1XFF), were used for docking studies of enzyme in R.oryzae by SchrödingerMaestro v9.1. To investigate binding between enzyme and inhibitors, Glide and Induced Fit docking were performed. IFD results of 1XFF with FMDP yielded C1, R73, W74, T76, G99 and D123 as the binding sites. C379 and Q427 appear to be vital for binding of R.oryzae enzymes to inhibitors. The comparison results of IFD scores of enzyme in R.oryzae and E.coli (PDBid: 2BPL) yield appreciable score, hinting at the probable effectiveness of inhibitors FMDP and ADGP against R.oryzae, with ADGP showing an improved enzyme affinity. Moreover, the two copies of gene G-6-P synthase due to extensive fungal gene duplication, in R. oryzae eliminating the problem of drug ineffectiveness could act as a potential antifungal drug target in R. oryzae with the application of peptide ligands.
authors.forename: Kamalika
authors.initials: K
authors.lastname: Banerjee
authors.forename: Utkarsh
authors.initials: U
authors.lastname: Gupta
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gupta
authors.forename: Gulshan
authors.initials: G
authors.lastname: Wadhwa
authors.forename: Reema
authors.initials: R
authors.lastname: Gabrani
authors.forename: Sanjeev Kumar
authors.initials: SK
authors.lastname: Sharma
authors.forename: Chakresh Kumar
authors.initials: CK
authors.lastname: Jain