Abstract
M2 proton channel of H1N1 Influenza A virus is the target protein anti-flu drugs amantadine and rimantadine. However, the two once powerful adamantane-based drugs lost their 90% bioactivity because of mutations of virus in recent twenty years. The resi stance of influenza A virus to amantadine need to d evelop more effective adamantane-based drugs. Several research by molecular docking method have been conducted to design and discover ligands which beco me potential inhibitors for the M2 channel protein of influenza virus in order to inhibit the replication of influenza virus. In this research are studied a nd evaluated the interaction of ligands towards the pr otein in the hydrated state using molecular dynamic s simulations at two different temperatures. Analysis of ligand interaction yields that AM-L6-R6 ligand has best affinity towards the protein than the T-R6-L6, T-L6-R12 and the standard ligand. It is shown by t he ligand interaction on the enzyme active site which remains to be formed during the simulation performe d. At the end of simulation temperature of 300 K, AM-L6-R6 ligand has a residue contact with the Arg45 an d formed hydrogen bond with Asp44. Then at the end of simulation temperature of 312 K, AM-L6-R6 ligands also could form a hydrogen bond with Asp44. Conformational changes of protein which occur during simulation showed the dynamicization of an protein in the presence of solvent and inhibitor.
Highlights
The outbreak of H1N1 influenza A virus is a pandemic of a new strain of influenza virus identified in April 2009 (Trifonov et al, 2009), commonly to as “swine flu”
M2 proton channel sequences were downloaded from Influenza Virus Resource database of the National Center for Biotechnology Information (NCBI)
M2 channel sequences downloaded from the Influenza Virus Resource database of the National Center for Biotechnology Information (NCBI)
Summary
The outbreak of H1N1 influenza A virus is a pandemic of a new strain of influenza virus identified in April 2009 (Trifonov et al, 2009), commonly to as “swine flu”. The M2 channel of the influenza A virus is a homotetrameric protein that contains three different kinds of Transmembrane (TM) four-helix channel with 97 residues per subunit, each of which comprises an intracellular C-terminal domain with a length of 54 residues, a transmembrane domain with a length of 19 residues and an extracellular N-terminal domain with a length of 24 residues (Holsinger and Lamb, 1991; Sugrue and Hay, 1991; Huang et al, 2008; Du et al, 2009; Intharathep et al, 2008) This protein has a major warning phase 6, meaning that the spread of H1N1 function as a proton-selective channel that is controlled
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