title: Molecular Dynamics Simulation of a RNA Aptasensor.
abstract: Single-stranded RNA aptamers have emerged as novel biosensor tools. However, the immobilization procedure of the aptamer onto a surface generally induces a loss of affinity. To understand this molecular process, we conducted a complete simulation study for the Flavin mononucleotide aptamer for which experimental data are available. Several molecular dynamics simulations (MD) of the Flavin in complex with its RNA aptamer were conducted in solution, linked with six thymidines (T6) and, finally, immobilized on an hexanol-thiol-functionalized gold surface. First, we demonstrated that our MD computations were able to reproduce the experimental solution structure and to provide a meaningful estimation of the Flavin free energy of binding. We also demonstrated that the T6 linkage, by itself, does not generate a perturbation of the Flavin recognition process. From the simulation of the complete biosensor system, we observed that the aptamer stays oriented parallel to the surface at a distance around 36 Å avoiding, this way, interaction with the surface. We evidenced a structural reorganization of the Flavin aptamer binding mode related to the loss of affinity and induced by an anisotropic distribution of sodium cationic densities. This means that ionic diffusion is different between the surface and the aptamer than above this last one. We suggest that these findings might be extrapolated to other nucleic acids systems for the future design of biosensors with higher efficiency and selectivity.
authors.affiliation: Université Paris Diderot , Sorbonne Paris Cité, ITODYS, UMR 7086, CNRS, 15 rue J-A de Baïf, 75013 Paris, France.|School of Materials and Metallurgy, Hubei Polytechnic University , Huangshi, Hubei, China.
authors.forename: Min
authors.initials: M
authors.lastname: Ruan
authors.affiliation: Université Paris Diderot , Sorbonne Paris Cité, ITODYS, UMR 7086, CNRS, 15 rue J-A de Baïf, 75013 Paris, France.
authors.forename: Mahamadou
authors.initials: M
authors.lastname: Seydou
authors.affiliation: Université Paris Diderot , Sorbonne Paris Cité, ITODYS, UMR 7086, CNRS, 15 rue J-A de Baïf, 75013 Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Noel
authors.affiliation: Université Paris Diderot , Sorbonne Paris Cité, ITODYS, UMR 7086, CNRS, 15 rue J-A de Baïf, 75013 Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Piro
authors.affiliation: Université Paris Diderot , Sorbonne Paris Cité, ITODYS, UMR 7086, CNRS, 15 rue J-A de Baïf, 75013 Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Maurel
authors.affiliation: Université Paris Diderot , Sorbonne Paris Cité, ITODYS, UMR 7086, CNRS, 15 rue J-A de Baïf, 75013 Paris, France.
authors.forename: Florent
authors.identifier: 0000-0002-6082-3194
authors.initials: F
authors.lastname: Barbault
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001665:Binding Sites; D015374:Biosensing Techniques; D005486:Flavin Mononucleotide / Q000737:chemistry*; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D013816:Thermodynamics
chemical_list: D052157:Aptamers, Nucleotide; D005486:Flavin Mononucleotide