Novel binding patterns between ganoderic acids and neuraminidase: Insights from docking,molecular dynamics and MM/PBSA studies |
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| Affiliation: | 1. Department of Applied Physics, Xi’an Jiaotong University, Xi’an 710049, PR China;2. School of Basic Medical Sciences, Jiamusi University, Jiamusi 154007, PR China;3. Institute of Biomedicine, Jinan University, Guangzhou 510632, PR China;1. College of Chemistry and Environmental Engineering, Yangtze University, Jingzhou 434023, China;2. School of Environmental and Municipal Engineering, Qingdao University of Technology, Qingdao 266033, China;3. School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, China;1. National Institute of Advanced Industrial Science and Technology (AIST), Nagoya 463-8560, Japan;2. Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, Sanda 669-1337, Japan;3. Department of Materials Science and Engineering, University of Delaware, Newark, DE 19716, USA;1. Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China;2. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China;3. Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650201, China;1. Laboratory of Marine Life Science and Technology, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang, China;2. School of Life Sciences, Shaoxing University, Shaoxing, Zhejiang, China;3. Ocean College, Qinzhou University, Qinzhou City, Guangxi, China |
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| 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. |
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| Keywords: | Neuraminidase Ganoderic acids Interactions Docking Molecular dynamics MM/PBSA |
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