Simulations of the dynamics at an RNA-protein interface.
Molecular dynamics simulations of the RNA-binding domain of the U1A spliceosomal protein in complex with its cognate RNA hairpin, performed at low and high ionic strength in aqueous solution, suggest a pathway for complex dissociation. First, cations condense around the RNA and compete with the protein for binding sites. Then solvated ions specifically destabilize residues at the RNA-protein interface. For a discrete cluster of residues at the complex interface, the simulations reveal an increased deviation from the crystal structure at high salt concentrations while the remaining protein scaffold is stabilized under these conditions. The microscopic picture of salt influence on the complex suggests guidelines for rational design of interface inhibitors targeted at RNA-protein complexes.
Hermann
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T
Institut de Biologie Moléculaire et Cellulaire du CNRS, UPR 9002, Equipe de Modélisation et Simulation des Acides Nucléiques, Strasbourg, France.
Westhof
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D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000187:drug effects; D003198:Computer Simulation; D017124:Conserved Sequence; D003460:Crystallization; D015195:Drug Design; D006860:Hydrogen Bonding; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009994:Osmolar Concentration; D017433:Protein Structure, Secondary / Q000187:drug effects; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000737:chemistry* / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D013816:Thermodynamics
D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; C075339:U1A protein; D012965:Sodium Chloride; D012313:RNA