Novel binding patterns between ganoderic acids and neuraminidase: Insights from docking, molecular dynamics and MM/PBSA studies
Novel binding patterns between ganoderic acids and neuraminidase: Insights from docking, molecular dynamics and MM/PBSA studies
复制标题
DOI：
10.1016/j.jmgm.2016.02.006
复制
发表时间：
2016-04-01
影响因子：
2.9
通讯作者：
Zhang, Shengli
中科院分区：
文献类型：
--
作者：
Yang, Zhiwei;Wu, Fei;Zhang, Shengli
近年来，灵芝酸（GAs）成为神经氨酸酶（NA）抑制剂的重要候选物。然而，关于它们的结合模式仍然没有明显的结论。为此，结合对接，分子动力学和MM/PBSA方法来研究GAs与N1蛋白和常见的H274 Y和N294 S突变（A/Vietnam/1203/04染色）的结合谱。发现灵芝酸DM和Z的结合亲和力（Δ G（结合），-16.83和-10.99 kcal mol（-1））与当前商业药物奥司他韦的结合亲和力（-23.62 kcal mol（-1））相当。静电相互作用是影响NA抑制剂结合的主要驱动力，应作为评价NA抑制剂结合质量和合理设计NA抑制剂的重要因素之一。150环残基Asp 151和Arg 152在结合过程中起重要作用。进一步的分析表明灵芝酸DM是一种潜在的抗流感成分，具有新的结合模式和优势，比奥司他韦。它对N1蛋白的150个空腔具有空间位阻作用，并对H274 Y和N294 S突变具有活性。本工作也为如何有效地设计双位点NA抑制剂和增强其亲和力指明了方向。这些发现对于深入了解NA和GAs之间的相互作用是有价值的，并且保证了设计新型抗流感药物的实验方面。(C)2016 Elsevier Inc. All rights reserved.
Recently, ganoderic acids (GAs) give rise to the attractive candidates of novel neuraminidase (NA) inhibitors. However, there is still no evident conclusion about their binding patterns. To this end, docking, molecular dynamics and MM/PBSA methods were combined to study the binding profiles of GAs with the N1 protein and familiar H274Y and N294S mutations (A/Vietnam/1203/04 stain). It was found that the binding affinities of ganoderic acid DM and Z (Delta G(bind),-16.83 and-10.99 kcal mol(-1)) are comparable to that of current commercial drug oseltamivir (-23.62 kcal mol(-1)). Electrostatic interaction is the main driving force, and should be one important factor to evaluate the binding quality and rational design of NA inhibitors. The 150-loop residues Asp151 and Arg152 played an important role in the binding processes. Further analysis revealed that ganoderic acid DM is a potential source of anti-influenza ingredient, with novel binding pattern and advantage over oseltamivir. It had steric hindrance on the 150 cavity of N1 protein, and exerted activities across the H274Y and N294S mutations. This work also pointed out how to effectively design dual-site NA inhibitors and reinforce their affinities. These findings should prove valuable for the in-depth understanding of interactions between NA and GAs, and warrant the experimental aspects to design novel anti-influenza drugs. (C) 2016 Elsevier Inc. All rights reserved.