Application of standard and enhanced sampling approaches on non-canonical structures of DNA and RNA

It has been widely demonstrated that both DNA and RNA nucleic acids can adopt also non-canonical higher-order structures called G-quadruplexes (G4s) formed by four guanines that can self-associate into a square-planar platform and π-stack upon each other forming the so called G-quartet [1-2]. Since such non-canonical structures are present in important regions of the human genome, both DNA and RNA G4s are considered as innovative targets for anticancer agents development. Here, we present two computational strategies recently performed on such non-canonical structures: the first consists in a Structure-based Virtual Screening method used to identify a novel dual binder of telomeric DNA and TERRA G4s [3], the two enhanced Metadynamics-based approaches were adopted to accurately investigate the ligand/DNA G-quadruplex binding [4-5] and retrieve the folding intermediate states of the parallel topology of the human telomeric DNA G4 [6].