Book of Abstracts: Albany 2011
June 14-18 2011
©Adenine Press (2010)
Insight into Transition States in Protein-RNA Recognition through MD Simulations
Protein-RNA recognition plays an important role in many post transcriptional-gene-expression-regulation, such as RNA modification, transportation, translation and degradation. U1A, a member of RNA Recognition Motif (RRM) containing protein family, is a component of an RNA-protein complex called U1A snRNP involved in pre-mRNA splicing. RRM proteins' abilities to recognize and bind to their cognate RNA sequence involves various nonbonding forces, such as electrostatic attraction, hydrogen bonding, aromatic stacking and van de Waals interactions. Results from our Molecular Dynamics (MD) studies on RRM containing proteins (U1A, SXL) and their cognate RNA sequences indicate that significant structural adaptations in both proteins and RNA sequences are required for binding. Simulations on mutant proteins demonstrate that electrostatics is the dominating force during the initial steps of the binding event. RMSD and RMSF analyses of the simulations indicate the free RMM containing proteins are more flexible than the protein-RNA complex for both U1A and SXL. Regions of the protein that undergo the greatest flexibility include N- and C-termini, loops and helixes. Covariance analyses indicate that a strong connectivity in a network of amino acids separated by long distances can be used to explain the mechanism of conformational change upon protein-RNA binding. PCA analyses and 3D-RMSD spaces are constructed to further identify the transition states of the binding events.
¹Department of Chemistry, Wesleyan University, Middletown, Connecticut