title: Molecular modeling and dynamics of the sodium channel inactivation gate.
abstract: The intracellular linker L(III-IV) of voltage-gated sodium channels is known to be involved in their mechanism of inactivation. Its primary sequence is well conserved in sodium channels from different tissues and species. However, the role of charged residues in this region, first thought to play an important role in inactivation, has not been well identified, whereas the IFM triad (I1488-M1490) has been characterized as the crucial element for inactivation. In this work, we constructed theoretical models and performed molecular dynamics simulations, exploring the role of L(III-IV)-charged residues in the presence of a polar/nonpolar planar interface represented by a dielectric discontinuity. From structural predictions, two alpha-helical segments are proposed. Moreover, from dynamics simulations, a time-conserved motif is detected and shown to play a relevant role in guiding the inactivation particle toward its receptor site.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho UFRJ - Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Fernanda L
authors.initials: FL
authors.lastname: Sirota
authors.forename: Pedro G
authors.initials: PG
authors.lastname: Pascutti
authors.forename: Celia
authors.initials: C
authors.lastname: Anteneodo
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015233:Models, Statistical; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D051381:Rats; D015222:Sodium Channels / Q000737:chemistry*; D013696:Temperature
chemical_list: D000596:Amino Acids; D015222:Sodium Channels