DNA produces a wide range of structures in addition to the canonical B-form of double-stranded DNA. Some of these structures are stabilized by Hoogsteen bonds. We developed an experimentally parameterized, coarse-grained model that incorporates such bonds. The model reproduces many of the microscopic features of double-stranded DNA and captures the experimental melting curves for a number of short DNA hairpins, even when the open state forms complicated secondary structures. We demonstrate the utility of the model by simulating the folding of a thrombin aptamer, which contains G-quartets, and strand invasion during triplex formation. Our results highlight the importance of including Hoogsteen bonding in coarse-grained models of DNA.
Bibliographical noteFunding Information:
We are grateful to Juan de Pablo and co-workers for their comments on an earlier version of this manuscript. This work was supported by a Career Development Award from the International Human Frontier Science Program Organization, the David and Lucile Packard Foundation and a Biotechnology Training Grant from the NIH (Grant No. 5T32GM008347-20).