Gene mutations influence the folding kinetics of hepatitis delta virus （HDV） ribozyme. In this work, we study the effect of the double mutation on the folding kinetics of HDV ribozyme. By using the master equation method combined with RNA folding free energy landscape, we predict the folding kinetics of C13A：G82U and A16U：U79A mutated HDV sequences. Their folding pathways are identified by recursively searching the states with high net flux-in（out） population starting from the native state. The results indicate that the folding kinetics of C 13A：G82U mutation sequence is bi-phasic, which is similar to the wild type （wtHDV） sequence. While the folding kinetics of A16U：U79A mutation sequence is mono-phasic, it quickly folds to the native state in 30 s. Thus, the folding kinetics of double mutated HDV ribozyme depends on the mutation sites.
A nucleotide base pair is the basic unit of RNA structures. Understanding the thermodynamic and kinetic properties of the closing and opening of a base pair is vital for quantitative understanding the biological functions of many RNA molecules. Due to the fast transition rate, it is difficult to directly observe opening and closing of single nucleic acid base pair in experiments. This review will provide a brief summary of the studies about the thermodynamic and kinetic properties of a base pair opening and closing by using molecular dynamic simulation methods.
