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Binding Drugs on Two Position of M2 Proton Channel and Its Mutants

Part of the IFMBE Proceedings book series (IFMBE, volume 49)

Abstract

M2 protein plays as an proton channel in influenza virus, and many candidates were proposed to inhibit its activity. Three new inhibitors were proposed recently by Du Q-S, et al. (2010), and their biding energy was higher than two commercial drug, Amantadine and Rimantadine. To investigate the potency of the new compound on drug-resistant variants, molecular docking was used to investigate how they bind in two positions of M2 proton channel and its mutants of H3N2 virus. The global docking on the M2 protein (residues 22-46) showed that the coexistence of two binding positions in NMR structure is possible, but the inhibitors favor the in pore position more than the outside of the pore. In the detail docking, mean binding energies of the new inhibitors were lower the commercial drugs, Rimantadine. The comparison between mean binding energy and intermolecular energy indicated that the torsional free energy has caused this decreasing energy. In another word, the adding new groups actually increase binding energy of inhibitors but it also makes them heavy and hard to rotate. In other hand, these new inhibitors were failed in binding on mutant D44A, and their binding energies were no different between wild type and mutants V27A, S31N and L26F. These mutants have suggested some hints to improve inhibitors’ structure, and chosen a choice about how these mutants resist the inhibitors.

Keywords

M2 channel mutants binding energy inhibitors drug resistance 

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Copyright information

© IFMBE 2013

Authors and Affiliations

  1. 1.Theoretical Physics DivisionUniversity of Science Ho Chi Minh CityHo Chi Minh CityVietnam
  2. 2.School of BiotechnologyHo Chi Minh International UniversityHo Chi Minh CityVietnam

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