A study of collective atomic fluctuations and cooperativity in the U1A-RNA complex based on molecular dynamics simulations.
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.
Kormos
Bethany L
BL
Chemistry Department and Molecular Biophysics Program, Wesleyan University, 237 Church St., Middletown, CT 06459, USA. bkormos@wesleyan.edu
Baranger
Anne M
AM
Beveridge
David L
DL
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*
D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; C075339:U1A protein; D012313:RNA