Molecular Docking On The Interacting Mechanisms Between Neuraminidases And 3-(3-pentyloxy) Benzoic Acid

Influenza is a respiratory illness which involves the upper respiratory tract, associated with the infection of influenza virus. Each year millions of people suffer from the infections. Recently, one sub-types of influenza virus A/H1N1 has spread on a world scale, caused by the significant morbidity and morality of virus for the general population. The World Health Organization (WHO) declares the influenza as one of the potential threats for human existence. Up to now, there is a lack of effective prevention and control methods against influenza virus. Therefore, the investigation of anti-influenza virus is a hot spot in current pharmaceutical research.Molecular docking is one of the approaches in computer-aided drug design, as well as the frontier of science projects for the world scale. It has the characteristics of cross-subject research. The computer mode identification and optimization technique are used to search the database in existence, the special molecule matches with the active site of specially designed target relating diseases in geometry and chemistry. With the aid of computer, it realizes the virtual screening. Virtual screening not only accelerates the process of new drug research and development, but also reduces the expense of biological experiments.With the aid of molecular docking and molecular dynamics methods, an in-depth investigation is carried out on the binding mechanisms of 4-(N-acetylamino)-5-guanidino-3-(3-pentyloxy) benzoic acid (BA) with various types of neuraminidases (N1, N2 and N9 subtypes and B type). It indicates that BA is docked to the various types of neuraminidases with similar mechanisms, albeit some differences exist in the binding poses. BA matches their active sites well and forms stable complexes. The largest binding affinities with N1, N2 and N9 subtypes and B type are calculated to be-295.12,-331.51,-158.64 and-253.33 kcal·mol-1, respectively. It suggests that BA has excellent inhibiting effects to all the studied neuraminidases. The further analyses reveal that strong electrostatic and H-bonding interactions exist between BA and the conserved key active-site residues instead of the facile-mutated ones, indicating that the inhibiting effects will not be influenced obviously by mutations. Accordingly, BA is a potential anti-influenza virus drug worthy of more attention. Combined with the previous studies, we point out how to modify the BA molecule in order to enhance the inhibiting effects to the neuraminidases.