A study on allosteric communication in U1A-snRNA binding interactions: network analysis combined with molecular dynamics data.

The allosteric regulation during the binding interactions between small nuclear RNAs (snRNAs) and the associated protein factors is critical to the function of spliceosomes in alternative RNA splicing. Although network models combined with molecular dynamics simulations have shown to be powerful tools for the analysis of protein allostery, the atomic-level simulations are, however, too expensive and with limited accuracy for the large-size systems. In this work, we use a residual network model combined with a coarse-grained Gaussian network model (GNM) to investigate the binding interactions between the snRNA and the human U1A protein which is a major component of the spliceosomal U1 small nuclear ribonucleoprotein particle, and to identify the residues that play an important role in the allosteric communication in U1A during this process. We also utilize the Girvan-Newman method to detect the structural organization in U1A-snRNA recognition and interactions. Our results reveal that: (Ι) not only the residues at the binding sites that are traditionally considered to play a major role in U1A-snRNA association, but those residues that are far away from the RNA binding interface participate in the U1A's allosteric signal transmission induced by the RNA binding; (Π) the structure of U1A protein is well organized with different communities acting different roles for its RNA binding and allosteric regulation. The study demonstrates that the combination of the residual network and elastic network models is an effective and efficient method which can be readily extended to the investigation of the allosteric communication for other macromolecular interaction systems.