Wuchty S, Fontana W, Hofacker I L, Schuster P
Institut für Theoretische Chemie, Universität Wien, Austria.
Biopolymers. 1999 Feb;49(2):145-65. doi: 10.1002/(SICI)1097-0282(199902)49:2<145::AID-BIP4>3.0.CO;2-G.
An algorithm is presented for generating rigorously all suboptimal secondary structures between the minimum free energy and an arbitrary upper limit. The algorithm is particularly fast in the vicinity of the minimum free energy. This enables the efficient approximation of statistical quantities, such as the partition function or measures for structural diversity. The density of states at low energies and its associated structures are crucial in assessing from a thermodynamic point of view how well-defined the ground state is. We demonstrate this by exploring the role of base modification in tRNA secondary structures, both at the level of individual sequences from Escherichia coli and by comparing artificially generated ensembles of modified and unmodified sequences with the same tRNA structure. The two major conclusions are that (1) base modification considerably sharpens the definition of the ground state structure by constraining energetically adjacent structures to be similar to the ground state, and (2) sequences whose ground state structure is thermodynamically well defined show a significant tendency to buffer single point mutations. This can have evolutionary implications, since selection pressure to improve the definition of ground states with biological function may result in increased neutrality.
本文提出了一种算法，用于严格生成最小自由能与任意上限之间的所有次优二级结构。该算法在最小自由能附近特别快。这使得能够有效地近似统计量，如配分函数或结构多样性的度量。低能量状态密度及其相关结构对于从热力学角度评估基态的定义明确程度至关重要。我们通过探索碱基修饰在tRNA二级结构中的作用来证明这一点，既在大肠杆菌单个序列层面，也通过比较具有相同tRNA结构的人工生成的修饰和未修饰序列的集合。两个主要结论是：（1）碱基修饰通过在能量上限制相邻结构与基态相似，从而显著锐化了基态结构的定义；（2）基态结构在热力学上定义明确的序列显示出显著的缓冲单点突变的倾向。这可能具有进化意义，因为改善具有生物学功能的基态定义的选择压力可能导致中性增加。
