Doctor Ivo Hofacker
Institut fuer Theoretische Chemie
Waehringerstrasse 17
1090 Wien, Austria

Monday, March 19, 2001
3:00 pm (CT)
3269 Beckman Institute

Abstract

The ability to fold into a well-defined native conformation is a prerequisite for biological functional biopolymers. In the case of RNA, secondary structures provide a computationally feasible model, in which most thermodynamic quantities of interest such as the ground state and partition function can be computed efficiently via dynamic programming. Such equilibrium properties are, however, not sufficient to characterize the folding behavior. To investigate the folding dynamics of an RNA sequence, we consider the energy landscape formed by all possible conformations (secondary structures). By enumerating all conformations within a predefined energy range, we obtain a detailed picture of the energy landscape in the vicinity of the ground state. In particular we are able to identify local minima, as well as measure their basins of attraction and the energy barriers separating them. This analysis of the landscape can be compared to detailed folding simulations using a Monte Carlo technique, as well as experimental data on some biologically relevant sequences. Folding kinetics depend strongly on the highest energy barrier present in the landscape, and barriers high enough to stabilize mis-folded states over biologically relevant times, can occur even for relatively short sequences. Such sequences can be design easily and may serve as molecular switches. Typical sequences exhibit a small number of significant local minima, which can be reached quickly from the unfolded state. For moderate length sequences the energy barriers between these local minima usually allow re-folding to the ground state.

Tea and coffee will be served in R3151 Beckman Institute at 2:15pm.