The design and synthesis of safe and efficient non-viral vectors for gene delivery has attracted significant attention in recent years.Previous experiments have revealed that the chemical structure of a polycation (the carrier) plays a crucial role in gene delivery system,e.g.strong interaction between carrier and nucleic acid may well hinder the release of the gene from the complex in the cytosol thereby adversely affecting transfection efficiency.Reliable binding free energy estimates may therefore be an effective index to estimate the ability of nucleic acids to dissociate from their carriers once in the cytosol.In this work,we adopt an atomistic molecular dynamics (MD) simulation approach to study the complexation of duplex RNA with six cationic carrier systems of varying surface topology.