Deciphering hydration patterns across RNA conformations: Insights into water-mediated RNA recognition

Area of Science:

• Biochemistry
• Structural Biology
• Computational Biology

Background:

• Water is essential for stabilizing ribonucleic acid (RNA) structures.
• The role of hydration in RNA binding specificity across different conformations is not well understood.
• The human immunodeficiency virus (Rev response element) RRE is a model system for studying RNA-protein interactions.

Purpose of the Study:

• To investigate how hydration patterns encode binding specificity in RNA.
• To understand the role of water in RNA molecular recognition across different conformations.
• To elucidate the mechanisms of RNA-peptide recognition, distinguishing between induced-fit and pre-organized pathways.

Main Methods:

• All-atom molecular dynamics simulations were used to map persistent water-binding sites.
• Hydrogen-bond lifetimes were quantified to analyze hydration dynamics.
• Three distinct RNA conformations (apo, Rev-binding, RSG 1.2-binding) were simulated.

Main Results:

• The apo state of RRE has a diffuse hydration shell stabilizing the backbone.
• The Rev-binding conformation shows a transient and reorganized hydration environment, indicating adaptive restructuring.
• The RSG 1.2-binding conformation maintains an ordered hydration scaffold, suggesting pre-organization.

Conclusions:

• Hydration patterns are key to RNA adaptability and recognition readiness.
• Water's role in RNA recognition dictates whether binding occurs via induced-fit or pre-organized mechanisms.
• Findings support thermodynamic analyses showing RRE-Rev binding is driven by solvent displacement and structural rearrangement, not just enthalpic contacts.