Gu Zonglin, De Luna Phil, Yang Zaixing, Zhou Ruhong
School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, 215123, China.
Computational Biological Center, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.
Phys Chem Chem Phys. 2017 Jan 25;19(4):3039-3045. doi: 10.1039/c6cp05260f.
Molybdenum disulfide (MoS) has recently emerged as a promising nanomaterial in a wide range of applications due to its unique and impressive properties. For example, MoS has gained attention in the biomedical field because of its ability to act as an antibacterial and anticancer agent. However, the potential influence of this exciting nanomaterial on biomolecules is yet to be extensively studied. Molecular dynamics (MD) simulations are invaluable tools in the examination of protein interactions with nanomaterials such as MoS. Previous protein MD studies have employed MoS force field parameters which were developed to accurately model bulk crystal structures and thermal heat transport but may not necessarily be amendable to its properties at the interface with biomolecules. By adopting a newly developed MoS force field, which was designed to better capture its interaction with water and proteins, we have examined the changes in protein structures between the original and refitted MoS force field parameters of three representative proteins, polyalanine (α-helix), YAP65 WW-domains (β-sheet), and HP35 (globular protein) when adsorbed onto MoS nanomaterials. We find that the original force field, with much larger van der Waals (vdW) contributions, resulted in more dramatic protein structural damage than the refitted parameters. Importantly, some denaturation of the protein tertiary structure and the local secondary structure persisted with the refitted force field albeit overall less severe MoS denaturation capacity was found. This work suggests that the denaturation ability of MoS to the protein structure is not as dire as previously reported and provides noteworthy findings on the dynamic interactions of proteins with this emergent material.
二硫化钼（MoS）因其独特且令人瞩目的特性，近来在广泛的应用领域中成为一种颇具前景的纳米材料。例如，MoS因其作为抗菌和抗癌剂的能力而在生物医学领域受到关注。然而，这种令人兴奋的纳米材料对生物分子的潜在影响尚未得到广泛研究。分子动力学（MD）模拟是研究蛋白质与诸如MoS等纳米材料相互作用的宝贵工具。先前的蛋白质MD研究采用了MoS力场参数，这些参数是为了精确模拟体相晶体结构和热传导而开发的，但不一定适用于其与生物分子界面处的性质。通过采用一种新开发的旨在更好地捕捉其与水和蛋白质相互作用的MoS力场，我们研究了三种代表性蛋白质，即聚丙氨酸（α-螺旋）、YAP65 WW结构域（β-折叠）和HP35（球状蛋白质）在吸附到MoS纳米材料上时，原始和重新拟合的MoS力场参数之间蛋白质结构的变化。我们发现，具有更大范德华（vdW）贡献的原始力场比重新拟合的参数导致更显著的蛋白质结构损伤。重要的是，尽管发现重新拟合的力场总体上MoS变性能力较弱，但蛋白质三级结构和局部二级结构的一些变性仍然存在。这项工作表明，MoS对蛋白质结构的变性能力并不像先前报道的那么严重，并提供了关于蛋白质与这种新兴材料动态相互作用的值得注意的发现。
