(156a) Coarse-Grained Modeling of the 10-23 DNAzyme

DNAzymes are single-stranded DNA that, depending on their sequence, catalyze cleavage, ligation or phosphorylation of nucleic acids. We are interested in correlating the diffusive fluctuations of DNAzymes and their substrates with the corresponding enzymatic activity. Diffusive fluctuations take place over millisecond time-scales, making them difficult to simulate using atomistic methods. We have adopted a simple physical model that captures, in a coarse-grained manner, the diffusive motion of single stranded DNA. We used this model to investigate the dynamics of the RNA cleaving 10-23 DNAzyme over long time scales via Brownian dynamics simulations. In our first study, we start from an unfolded state where the DNAzyme is bound to the substrate and allow the system to relax. The structural data thus obtained agree well with FRET measurements and provide a connection between the proposed structure of the DNAzyme and chemical rate data appearing in the literature. In a companion study, we have also investigated the mechanism of binding between the DNAzyme and a substrate, starting with both molecules unbound and a relaxed state. The latter simulations furnish insights into the physicochemical factors that govern substrate recognition and the eventual formation of the active state.