title: Molecular dynamics simulation of hepatitis C virus IRES IIId domain: structural behavior, electrostatic and energetic analysis.
abstract: The dynamic behavior of the HCV IRES IIId domain is analyzed by means of a 2.6-ns molecular dynamics simulation, starting from an NMR structure. The simulation is carried out in explicit water with Na+ counterions, and particle-mesh Ewald summation is used for the electrostatic interactions. In this work, we analyze selected patterns of the helix that are crucial for IRES activity and that could be considered as targets for the intervention of inhibitors, such as the hexanucleotide terminal loop (more particularly its three consecutive guanines) and the loop-E motif. The simulation has allowed us to analyze the dynamics of the loop substructure and has revealed a behavior among the guanine bases that might explain the different role of the third guanine of the GGG triplet upon molecular recognition. The accessibility of the loop-E motif and the loop major and minor groove is also examined, as well as the effect of Na+ or Mg2+ counterion within the simulation. The electrostatic analysis reveals several ion pockets, not discussed in the experimental structure. The positions of these ions are useful for locating specific electrostatic recognition sites for potential inhibitor binding.
authors.affiliation: Laboratoire Arômes Synthèses Interactions, Faculté des Sciences de Nice Sophia-Antipolis, 06108 cedex 2, Nice, France. Jerome.Golebiowski@unice.fr
authors.forename: Jérôme
authors.initials: J
authors.lastname: Golebiowski
authors.forename: Serge
authors.initials: S
authors.lastname: Antonczak
authors.forename: Audrey
authors.initials: A
authors.lastname: Di-Giorgio
authors.forename: Roger
authors.initials: R
authors.lastname: Condom
authors.forename: Daniel
authors.initials: D
authors.lastname: Cabrol-Bass
mesh_terms: D020816:Amino Acid Motifs; D001483:Base Sequence; D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006147:Guanine / Q000737:chemistry; D016174:Hepacivirus / Q000378:metabolism*; D006860:Hydrogen Bonding; D007477:Ions; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008956:Models, Chemical; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012367:RNA, Viral; D012270:Ribosomes / Q000737:chemistry*; D012964:Sodium / Q000737:chemistry; D055672:Static Electricity; D014867:Water / Q000737:chemistry
chemical_list: D002241:Carbohydrates; D007477:Ions; D012367:RNA, Viral; D014867:Water; D006147:Guanine; D012964:Sodium