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

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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 43A2 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.

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Acknowledgments

GRK, SS and NG wants to thanks University Grants Commission, Government of India for financial support and the School of Biochemical Engineering, Institute of Technology, BHU, Varanasi, India. KS wishes to thank Council of Scientific & Industrial Research, Government of India for providing financial assistance. SL wants to thank Indian Council of Medical Research (ICMR),New Delhi, Government of India for financial support and Tumour Biology Laboratory, National Institute of Pathology, Safdarjung Hospital Campus, New Delhi-110029 and RSC, CM gratefully acknowledges University Grant Commission (UGC), New Delhi (F.No.33-222/2007 (SR) 13-3-08) for financial support. The encouragement given by Sri Krishnadevaraya University, AP, India to our research work is gratefully acknowledged.

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Authors and Affiliations

  1. School of Biochemical Engineering, Institute of Technology, Banaras Hindu University, Varanasi, 221005, India

    Gundampati Ravi Kumar, Neeraj Gupta & Mira Debnath Das

  2. DBT-Bioinformatics Infrastructure Facility (BIF), Department of Biochemistry, Sri Krishna Devaraya University, Anantapur, 515003, India

    Rajasekhar Chikati, Chaitanya Mulakayala & Chitta Suresh Kumar

  3. Tumour Biology Laboratory, National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi, 110029, India

    Santhi Latha Pandrangi & Sunita Saxena

  4. Molecular Biology Unit, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India

    Kirti Sonkar & Medicherla V. Jagannadham

  5. Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117576, Singapore

    Manoj Kandapal

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  1. Gundampati Ravi Kumar
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  2. Rajasekhar Chikati
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  3. Santhi Latha Pandrangi
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  4. Manoj Kandapal
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  8. Medicherla V. Jagannadham
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  9. Chitta Suresh Kumar
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  10. Sunita Saxena
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  11. Mira Debnath Das
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Correspondence to Mira Debnath Das.

Additional information

Gundampati Ravi Kumar, Rajasekhar Chikati and Santhi Latha Pandrangi contributed equally to this work.

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Kumar, G.R., Chikati, R., Pandrangi, S.L. et al. Molecular docking and dynamics simulations of A.niger RNase from Aspergillus niger ATCC26550: for potential prevention of human cancer. J Mol Model 19, 613–621 (2013). https://doi.org/10.1007/s00894-012-1587-9

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  • DOI: https://doi.org/10.1007/s00894-012-1587-9

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