title: 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.
authors.affiliation: School of Biochemical Engineering, Institute of Technology, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Gundampati Ravi
authors.initials: GR
authors.lastname: Kumar
authors.forename: Rajasekhar
authors.initials: R
authors.lastname: Chikati
authors.forename: Santhi Latha
authors.initials: SL
authors.lastname: Pandrangi
authors.forename: Manoj
authors.initials: M
authors.lastname: Kandapal
authors.forename: Kirti
authors.initials: K
authors.lastname: Sonkar
authors.forename: Neeraj
authors.initials: N
authors.lastname: Gupta
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Mulakayala
authors.forename: Medicherla V
authors.initials: MV
authors.lastname: Jagannadham
authors.forename: Chitta Suresh
authors.initials: CS
authors.lastname: Kumar
authors.forename: Sunita
authors.initials: S
authors.lastname: Saxena
authors.forename: Mira Debnath
authors.initials: MD
authors.lastname: Das
mesh_terms: D000199:Actins / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001234:Aspergillus niger / Q000737:chemistry* / Q000201:enzymology; D001665:Binding Sites; D001943:Breast Neoplasms / Q000517:prevention & control; D002277:Carcinoma / Q000517:prevention & control; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005656:Fungal Proteins / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D012260:Ribonucleases / Q000737:chemistry* / Q000494:pharmacology; D013816:Thermodynamics; D014410:Tumor Stem Cell Assay
chemical_list: D000199:Actins; D000970:Antineoplastic Agents; D005656:Fungal Proteins; D012260:Ribonucleases