The major goal of research in Dr. Serra's lab is the development of models to predict the stability of RNA structure from its sequence. To do this, small synthetic RNA oligomers are studied by optical melting to determine their thermodynamic stability. The effect of sequence on the stability of the RNA is used to develop models to predict the structure of naturally occurring RNAs.

Structural characteristics of specific RNA sequences can be analyzed by spectroscopy. Specifically, a UV-Visible spectrophotometer can be used to measure the absorbance of the RNA solution as the temperature of that solution is changed at a well-defined rate. This kind of study is referred to as an optical melting experiment because the measurement is performed by optical means (the spectrophotometer) during the thermal melting of the RNA.

Take a moment to view a graphical representation of an optical melting experiment.
Note the following occurances in the presentation:

1. As the temperature of the RNA solution increases, its absorbance increases as well (i.e. transmittance decreases).
2. The increase in temperature causes the structured RNA molecule to "melt" into a disordered RNA strand.
3. A plot of absorbance vs. temperature (usually) gives a graph which can be used to determine information about the thermodynamic stability of the RNA sequence.

Related research of RNA sequences involves the addition of magnesium to the buffer solution containing the RNA. Experiments have shown that magnesium increases the thermodynamic stability of RNA stuctures. Several models have been proposed to explain the increased stability. Three of these models are represented below.

In all representaions, some of the magnesium has bound to certain sites on the RNA strands.

Explanation 1: Two strands of RNA collide and bind to each other. This increases the charge density of the RNA, allowing more Mg from the solution to bind to the RNA. Because more Mg atoms have found favorable binding sites, the energy of the system is decreased and the RNA strands are therefore held together with more stability. View

Explanation 2: As the two strands of RNA collide, the magnesium bound to each individual strand finds sites that are even more preferential. That is, the RNA-Mg attraction increases as the RNA strands come together. View

Explanation 3: As the two strands of RNA collide, specific sites are formed between the two strands which are much more favorable binding sites for the magnesium. Thus the RNA-Mg attraction increases at these sites.
    Version A - Two strands View
    Version B - One strand View

Brownian-Dynamics Simulations

Here is a demonstration of the method Thomas Hermann and Eric Westhof are using to gain information about metal ion binding sites in RNA folds using Brownian-dynamics simulations. View