THE COMPUTER-SIMULATION OF RNA FOLDING PATHWAYS USING A GENETIC ALGORITHM

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.