Description of RNA folding by ''simulated annealing''

An algorithm is proposed which describes the thermodynamically as well as the kinetically controlled folding process of RNA. The algorithm, based on a special Monte Carlo procedure known as ''Simulated Annealing'', takes into account the probabilities for opening and closing of single base-pairs. Thus, the algorithm is able to reach structures and structure distributions near the global minimum of structure space, and is not restricted by the tendency to halt in local minima. Three types of structural folding processes may be analysed by this algorithm. Firstly, using thermodynamic data, structure ensembles comparable to those obtained by dynamic programming are achieved. Secondly, using kinetic data, the processes of structure formation and structural rearrangement may be simulated. Thirdly, additionally taking into account RNA polymerase chain elongation rates, the process of ''sequential foldin'' during transcription may be described. Analysis of all types of structural folding and refolding is performed for RNA sequences related to potato spindle tuber viroid (PSTVd). The computed results are in accordance with experimental data and biological functions known for PSTVd. (C) 1996 Academic Press Limited