title: A molecular dynamics study of an L-type calcium channel model.
abstract: In this work, we propose a molecular model of the L-type calcium channel pore from the human cardiac alpha1 subunit. Four glutamic acid residues, the EEEE locus, located at highly conserved P loops (also called SS1-SS2 segments) of the alpha1 subunit, molecularly express the calcium channel selectivity. The proposed alpha-helix structure for the SS1 segment, analyzed through molecular dynamics simulations in aqueous-phase, was validated by the plotting of Ramachandran diagrams for the averaged structures and by the analysis of i and i + 4 helical hydrogen bonding between the amino acid residues. The results of the simulation of the calcium channel model with one and two Ca2+ ions at the binding site are in accordance with mutation studies which suggest that the EEEE locus in the L-type calcium channel must form a single high-affinity binding site. These results suggest that the Ca2+ permeation through the channel would be derived from competition between two ions for the only high-affinity binding site. Furthermore, the experimentally observed blocking of the Na+ flux at micromolar Ca2+ concentrations, probably due to the occupancy of the single high-affinity binding site for one Ca2+, was also reproduced by our model.
authors.affiliation: Physical Organic Chemistry Group, Departamento de Química Orgânica, Instituto de Química, UFRJ, Bloco A, sala 609, Cidade Universitária,Ilha do Fundão, CT, RJ 21949-900, Rio de Janeiro, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Barreiro
authors.forename: Cristiano Ruch Werneck
authors.initials: CR
authors.lastname: Guimarães
authors.forename: Ricardo Bicca
authors.initials: RB
authors.lastname: de Alencastro
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
chemical_list: D020746:Calcium Channels, L-Type; D002118:Calcium