Due to the complex nature of the transitional phenomena under study, experiment and theory often have to go hand in hand in unraveling details of the microscopic forces involved (see abstracts below). For structural determination, the initial "guess" structure is usually obtained from theory. Of special interest to us is the study of biological structural changes free of the effects of solvent. Theory is a guiding force when considering the myriad of structural configurations and the unique features of diffraction. For example, in order to investigate the unfolding of a helix-rich protein upon a rapid temperature jump, we must take into account all possible final conformations. This complexity may, naively, suggest the masking of any significant change in diffraction. However, an accurate theoretical mapping of helix-to-coil transitions in a large molecular ensemble indicates that the problem of tracking down the disruption of the helical ordering in space and time is tractable.

One of the major areas of focus in our research is that of the experimental and theoretical studies of phase transitions. Even for a small macromolecule, such as a DNA hairpin, the complexity of the energy landscape of folding-unfolding demands new tools of computations. Stimulated by recent observations of collapsed intermediate states for a DNA hairpin, we performed extensive MD simulations on a similar, benchmark DNA hairpin. But, concurrently, we developed an analytical model of DNA unzipping based on tabulated pairing-stacking thermodynamic parameters and loop entropy. After verifying the assumptions and predictions of the model via ensemble-convergent MD simulations, the model was used to determine the temperature range for which the two-state hypothesis breaks down as well as base-pairing structures of intermediates in the DNA (un)folding.