title: Novel binding patterns between ganoderic acids and neuraminidase: Insights from docking, molecular dynamics and MM/PBSA studies.
abstract: 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 (ΔGbind, -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.
authors.affiliation: Department of Applied Physics, Xi'an Jiaotong University, Xi'an 710049, PR China; School of Basic Medical Sciences, Jiamusi University, Jiamusi 154007, PR China. Electronic address: yzws-123@163.com.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Yang
authors.affiliation: School of Basic Medical Sciences, Jiamusi University, Jiamusi 154007, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wu
authors.affiliation: Institute of Biomedicine, Jinan University, Guangzhou 510632, PR China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Applied Physics, Xi'an Jiaotong University, Xi'an 710049, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Applied Physics, Xi'an Jiaotong University, Xi'an 710049, PR China. Electronic address: zhangsl@xjtu.edu.cn.
authors.forename: Shengli
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry*; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry*; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry* / Q000201:enzymology; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009154:Mutation; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D053139:Oseltamivir / Q000737:chemistry*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D055672:Static Electricity; D013816:Thermodynamics; D014315:Triterpenes / Q000737:chemistry*; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D014315:Triterpenes; D014764:Viral Proteins; C556862:ganoderic acid; D053139:Oseltamivir; D009439:Neuraminidase
keywords: Docking; Ganoderic acids; Interactions; MM/PBSA; Molecular dynamics; Neuraminidase