Gultyaev A P, van Batenburg F H, Pleij C W
Institute of Theoretical Biology, Leiden University, The Netherlands.
J Mol Biol. 1995 Jun 30;250(1):37-51. doi: 10.1006/jmbi.1995.0356.
A procedure for simulating the RNA folding process using the principles of genetic algorithm is proposed. The method allows one to simulate a folding pathway of RNA, including such processes as disruption of temporarily formed structures, the folding of a molecule during its synthesis and pseudoknot formation. The simulations are able to predict functional metastable foldings and kinetically driven transitions to more stable structures. The analysis of free energies for intermediate foldings allows estimation of the ranges of kinetic refolding barriers and suggests that in some RNAs the selective evolutionary pressure suppresses the possibilities for alternative structures that could form in the course of transcription. It is shown that the folding pathway simulation can result in structure predictions that are more consistent with phylogenetically proven structures than minimum energy solutions. This suggest that RNA folding kinetics is very important for the formation of functional RNA structures. Therefore, apart form its value for predictions of RNA structures, the proposed computer simulations can be a powerful tool in the studies of RNA folding features.
提出了一种利用遗传算法原理模拟RNA折叠过程的方法。该方法能让人模拟RNA的折叠途径，包括诸如临时形成结构的破坏、分子在合成过程中的折叠以及假结形成等过程。这些模拟能够预测功能性亚稳态折叠以及向更稳定结构的动力学驱动转变。对中间折叠的自由能分析允许估计动力学重折叠障碍的范围，并表明在一些RNA中，选择性进化压力抑制了转录过程中可能形成的替代结构的可能性。结果表明，与最小能量解相比，折叠途径模拟能够产生与系统发育证实的结构更一致的结构预测。这表明RNA折叠动力学对于功能性RNA结构的形成非常重要。因此，除了其在预测RNA结构方面的价值外，所提出的计算机模拟可以成为研究RNA折叠特征的有力工具。
