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: K homology (KH) domain, molecular dynamics (MD), neuro-oncological ventral antigen (NOVA), relationship between structure and function, RNA-binding protein (RBP), stabilization of protein, molecular dynamics, neurooncological ventral antigen, solvent accessible surface area, RBP-RNA complex, paraneoplastic opsoclonus-myoclonus ataxia, canonical RNA binding domain, pyrimidine, α-helix, β-strand, Molecular Dynamics Simulation, TIP3P water model, SHAKE program, Visual Molecular Dynamics, Nucplot analysis, enthalpy, entropy, Solvation energy, Ura12, Cyt13, Ade14, Cyt15, NOVA-RNA complex, RNA-protein recognition, paraneoplastic antibodies
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