Spontaneous Adjustment Mechanism in an RNA-Binding Protein: Cooperation Between Energetic Stabilization and Target Search Enhancement
Abstract:We propose a novel concept associated with the relationship between structure and function in biomolecular systems. We performed a 75 nanoseconds molecular dynamics (MD) simulation for an RNA-binding protein, neurooncological ventral antigen (NOVA), and examined its physico-chemical properties. NOVA dissociated from the NOVARNA complex showed a large conformational change: formation of intra-molecular hydrogen bonds between the Cterminal region and the loop structure located at the middle of amino acid sequence. The free energy analysis suggests that the deformed structure is more stabilized in macromolecular crowding environment where the dielectric constant is smaller than 5. The solvent accessible surface area (SASA) analysis indicates that NOVA enhances the efficiency of association with RNA by changing the relative SASA for the target sequence in RNA molecules. Based on the obtained results, we propose a novel concept of spontaneous adjustment mechanism to explain the structural and energetic changes observed for NOVA in the free state.
Keywords: Ade14; Cyt13; Cyt15; K homology (KH) domain; Molecular Dynamics Simulation; NOVA-RNA complex; Nucplot analysis; RBP-RNA complex; RNA-binding protein (RBP); RNA-protein recognition; SHAKE program; Solvation energy; TIP3P water model; Ura12; Visual Molecular Dynamics; canonical RNA binding domain; enthalpy; entropy; molecular dynamics; molecular dynamics (MD); neuro-oncological ventral antigen (NOVA); neurooncological ventral antigen; paraneoplastic antibodies; paraneoplastic opsoclonus-myoclonus ataxia; pyrimidine; relationship between structure and function; solvent accessible surface area; stabilization of protein; α-helix; β-strand
Document Type: Research Article
Publication date: 2010-12-01
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