Molecular docking and dynamics simulations of A.niger RNase from Aspergillus niger ATCC26550: for potential prevention of human cancer

Abstract

The aim of the present research was to study the anticancer effects of Aspergillus niger (A.niger) RNase. We found that RNase (A.niger RNase) significantly and dose dependently inhibited invasiveness of breast cancer cell line MDA MB 231 by 55 % (P<0.01) at 1 μM concentration. At a concentration of 2 μM, the anti invasive effect of the enzyme increased to 90 % (P<0.002). Keeping the aim to determine molecular level interactions (molecular simulations and protein docking) of human actin with A.niger RNase we extended our work in-vitro to in-silico studies. To gain better relaxation and accurate arrangement of atoms, refinement was done on the human actin and A.niger RNase by energy minimization (EM) and molecular dynamics (MD) simulations using 43A(2) force field of Gromacs96 implemented in the Gromacs 4.0.5 package, finally the interaction energies were calculated by protein-protein docking using the HEX. These in vitro and in-silico structural studies prove the effective inhibition of actin activity by A.niger RNase in neoplastic cells and thereby provide new insights for the development of novel anti cancer drugs.

Human RNASET2 derivatives as potential anti-angiogenic agents: actin binding sequence identification and characterization

“…However, we have shown that their actin binding capacity is essential. In line with our previous reports, we demonstrate herein that trT2-50m lacking the previously reported putative actin binding peptide [26,27] and the newly designed peptides based on hRNASET2 structure are able to bind actin and concomitantly inhibit angiogenesis. Actin binding ability was demonstrated using the immobilized actin solid phase assay and the BIAcore system.…”

“…Based on Gundampati et al 2012, and Kumar et al 2013 [26,27] findings who claimed that they have identified the actin-binding sequence of ACTIBIND we subsequently searched for an homologous sequence in the human RNASET2 sequence and identified it. We then generated a peptide library containing 29 peptides based on this sequence and based on structural analysis.…”

“…Gundampati et al 2012, and Kumar et al 2013 [26,27] examined the mechanism associated with binding of ACTIBIND to human actin using in vitro and in silico studies. The docking of ACTIBIND and actin revealed that the amino acids T L D S Y T A L S D A G I T P S E D A T Y K play a role in actin binding.…”

Exploration of anti-Malassezia potential of Nyctanthes arbor-tristis L. and their application to combat the infection caused by Mala s1 a novel allergen

“…Further, docking was performed between protein and active molecules (β-Sitosterol and Calceolarioside A) using Hex server and their interaction energies were analyzed (Tables 2 and 3 ). The low energies ensured efficient docking and also revealed that the protein could form hydrogen bond networks involving various active amino acid residues [ 52 ]. Figure 11 reveals various residues that exclusively contribute towards the binding of the protein with the natural molecules.…”

Fungal proteinaceous compounds with multiple biological activities

“…A. niger RNase at 1 μM and 2 μM reduced invasiveness of MDA-MB 231 breast cancer cells by half and 90 %, respectively. The aforementioned information may be useful for designing new antineoplastic medications (Gundampati et al 2012;Kumar et al 2013). Hirsutellin A is a cyclizing ribonuclease with 130 amino acids from the mite fungal pathogen Hirsutella.…”