Probing the Degree of Restriction in Solvent Dynamics at the Interface of a Protein-RNA Complex

Protein-RNA complexation is an important step for the regulation of numerous biological processes. Water present at the interface of a protein-RNA complex plays a critical role in guiding its structure, stability, and function. Therefore, studying the microscopic properties of interfacial water is essential to gain molecular insights into the formation of such complexes. In this study, we present results obtained from molecular dynamics (MD) simulations of poly(A)-binding protein (PABP) bound with poly(A) RNA, which is an essential regulatory step to control the deadenylation process, thereby stabilizing cellular mRNAs from degradation. Efforts have been made to explore how such complexation alters the regular dynamical and hydrogen bond properties of water present at the interface. The calculations revealed restricted water dynamics at the interface, characterized by heterogeneous time scales, with the extent of restriction being more pronounced for residues directly involved in protein-RNA binding. In particular, water molecules around the protein's linker, RRM2, and the RNA strand exhibit significantly more restricted motion compared to RRM1 upon complexation. Further, longer relaxation times of hydrogen bonds at the interface due to complex formation have been found to be correlated with increasingly restricted water motions. Notably, the kinetics of hydrogen bonds around the protein's linker, RRM2, and the RNA strand are more strongly influenced by complex formation, underscoring their critical role in mediating protein-RNA interactions.