title: A study of collective atomic fluctuations and cooperativity in the U1A-RNA complex based on molecular dynamics simulations.
abstract: Cooperative interactions play an important role in recognition and binding in macromolecular systems. In this study, we find that cross-correlated atomic fluctuations can be used to identify cooperative networks in a protein-RNA system. The dynamics of the RRM-containing protein U1A-stem loop 2 RNA complex have been calculated theoretically from a 10 ns molecular dynamics (MD) simulation. The simulation was analyzed by calculating the covariance matrix of all atomic fluctuations. These matrix elements are then presented in the form of a two-dimensional grid, which displays fluctuations on a per residue basis. The results indicate the presence of strong, selective cross-correlated fluctuations throughout the RRM in U1A-RNA. The atomic fluctuations correspond well with previous biophysical studies in which a multiplicity of cooperative networks have been reported and indicate that the various networks identified in separate individual experiments are fluctuationally correlated into a hyper-network encompassing most of the RRM. The calculated results also correspond well with independent results from a statistical covariance analysis of 330 aligned RRM sequences. This method has significant implications as a predictive tool regarding cooperativity in the protein-nucleic acid recognition process.
authors.affiliation: Chemistry Department and Molecular Biophysics Program, Wesleyan University, 237 Church St., Middletown, CT 06459, USA. bkormos@wesleyan.edu
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Kormos
authors.forename: Anne M
authors.initials: AM
authors.lastname: Baranger
authors.forename: David L
authors.initials: DL
authors.lastname: Beveridge
mesh_terms: D000595:Amino Acid Sequence; D003198:Computer Simulation; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012313:RNA / Q000737:chemistry*; D016601:RNA-Binding Proteins / Q000737:chemistry*; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000737:chemistry*
chemical_list: D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; C075339:U1A protein; D012313:RNA