(736g) A Multi-Scale Approach to the 10-23 DNAzyme

We will present a series of multi-scale simulations concerning the dynamic structures of the 10-23 DNAzyme. Deoxyribozymes (DNAzymes) are a new class of small catalytic oligodeoxynucleotides composed entirely of DNA. The 10-23 class of DNAzymes consists of a conserved 15-base catalytic core that is flanked by binding arms typically 7-10 bases in length with sequence complementary to the target single-stranded RNA. The 10-23 DNAzyme is capable of cleaving at a purine-pyrimidine junction with both high turnover rate and and substrate affinity, making it useful in a variety of applications. We employed a sequential Brownian Dynamics to Molecular Dynamics (BD2MD) method to develop an atomic-level prediction of the 10-23 DNAzyme structure, which cannot be obtained by crystallization. Starting from a naive guess for the structure of the DNAzyme bound to its substrate, we performed long-time simulations using a two-bead BD model to arrive at a coarse-grained structure. The BD result served as the input to a series of increasingly refined MD models that eventually included explicit solvent and ions. This incremental approach allowed us to capture the salient features of the secondary and tertiary structures of the 10-23 DNAzyme complex.