School of Biochemical Engineering, Institute of Technology, Banaras Hindu University, Varanasi, 221005, India.
J Mol Model. 2013 Feb;19(2):613-21. doi: 10.1007/s00894-012-1587-9. Epub 2012 Sep 16.
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.
本研究旨在研究黑曲霉核糖核酸酶（A.niger RNase）的抗癌作用。我们发现 RNase（黑曲霉 RNase）在 1 μM 浓度时，能显著且剂量依赖性地抑制乳腺癌细胞系 MDA MB 231 的侵袭性，抑制率为 55%（P<0.01）。当浓度为 2 μM 时，酶的抗侵袭作用增加到 90%（P<0.002）。为了确定人肌动蛋白与黑曲霉 RNase 的分子水平相互作用（分子模拟和蛋白质对接），我们将体外工作扩展到计算机模拟研究。为了更好地松弛和精确排列原子，我们使用 Gromacs96 中的 43A(2)力场对人肌动蛋白和黑曲霉 RNase 进行了能量最小化（EM）和分子动力学（MD）模拟，最终使用 HEX 进行蛋白质-蛋白质对接计算了相互作用能。这些体外和计算机模拟结构研究证明了黑曲霉 RNase 有效抑制肿瘤细胞中肌动蛋白的活性，从而为开发新型抗癌药物提供了新的见解。
