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 Annealin g'', takes into account the probabilities for opening and closing of s ingle base-pairs. Thus, the algorithm is able to reach structures and structure distributions near the global minimum of structure space, an d is not restricted by the tendency to halt in local minima. Three typ es of structural folding processes may be analysed by this algorithm. Firstly, using thermodynamic data, structure ensembles comparable to t hose obtained by dynamic programming are achieved. Secondly, using kin etic data, the processes of structure formation and structural rearran gement 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 str uctural folding and refolding is performed for RNA sequences related t o potato spindle tuber viroid (PSTVd). The computed results are in acc ordance with experimental data and biological functions known for PSTV d. (C) 1996 Academic Press Limited