Electrostatic Interaction Effects on the Binding of Spliceosomal U1A Protein-SL2 RNA Hairpin

The U1A protein is a component of the U1 small nuclear ribonucleoprotein particle, which forms part of the spliceosome. Since U1A protein is highly charged, electrostatic interactions have been suggested to be of importance in the association of the protein with RNA and the stability of the complex. To understand this effect, positively charged residues of the protein have been mutated in three positions (K20, K22 and K50) that do not have direct interactions with the SL2 RNA.We performed extensive molecule dynamics simulations on the mutant complexes and characterized the changes in the networks of interactions.To reveal more global variations within the mutant complexes, we also determined the changes on the subsections of the proteins-RNA (called communities) that move in concert together. These communities have been calculated based on generalized correlations to account for the collective atomic fluctuations within the protein-RNA complexes. These results are in agreement with the experimental complex dissociation binding studies.We then determined a measure based on the collective atomic fluctuations of different mutant complexes that have a linear correlation with the experimentally measured dissociation constants. This correlation can be used to further predict the effect of a mutation on the dissociation constant of the U1A-SL2 RNA complexes.