Steered molecular dynamics approach for promising drugs for influenza A virus targeting M2 channel proteins.

We have used steered molecular dynamics simulation to investigate the molecular interactions between four M2 inhibitors (amantadine, rimantadine, and two other amantadine derivatives) and the M2 protein channels of influenza A virus H5N1, including the wild type (WT) and three previously identified drug-resistant variants (G34A, S31N, and V27A). The binding free energies between these four inhibitors and the M2 channel of the WT and the three mutants were also determined by use of the molecular mechanics-Poisson-Boltzmann surface area method. Our study provides important insight into binding affinity, including detailed energy components and interactions at the molecular level of four potential inhibitors with the M2 channel of drug-resistant strains; this may assist further experimental study and strategies for rational design of new inhibitors.