A procedure for simulating the RNA folding process using the principle
s of genetic algorithm is proposed. The method allows one to simulate
a folding pathway of RNA, including such processes as disruption of te
mporarily formed structures, the folding of a molecule during its synt
hesis and pseudoknot formation. The simulations are able to predict fu
nctional metastable foldings and kinetically driven transitions to mor
e stable structures. The analysis of free energies for intermediate fo
ldings allows estimation of the ranges of kinetic refolding barriers a
nd suggests that in some RNAs the selective evolutionary pressure supp
resses the possibilities for alternative structures that could form in
the course of transcription. It is shown that the folding pathway sim
ulation can result in structure predictions that are more consistent w
ith phylogenetically proven structures than minimum energy solutions.
This suggest that RNA folding kinetics is very important for the forma
tion of functional RNA structures. Therefore, apart form its value for
predictions of RNA structures, the proposed computer simulations ran
be a powerful tool in the studies of RNA folding features.