Ward Max, Datta Amitava, Wise Michael, Mathews David H
Computer Science & Software Engineering, The University of Western Australia, Australia.
The Marshall Centre for Infectious Diseases Research and Training, The University of Western Australia, Australia.
Nucleic Acids Res. 2017 Aug 21;45(14):8541-8550. doi: 10.1093/nar/gkx512.
Algorithmic prediction of RNA secondary structure has been an area of active inquiry since the 1970s. Despite many innovations since then, our best techniques are not yet perfect. The workhorses of the RNA secondary structure prediction engine are recursions first described by Zuker and Stiegler in 1981. These have well understood caveats; a notable flaw is the ad-hoc treatment of multi-loops, also called helical-junctions, that persists today. While several advanced models for multi-loops have been proposed, it seems to have been assumed that incorporating them into the recursions would lead to intractability, and so no algorithms for these models exist. Some of these models include the classical model based on Jacobson-Stockmayer polymer theory, and another by Aalberts and Nadagopal that incorporates two-length-scale polymer physics. We have realized practical, tractable algorithms for each of these models. However, after implementing these algorithms, we found that no advanced model was better than the original, ad-hoc model used for multi-loops. While this is unexpected, it supports the praxis of the current model.
自20世纪70年代以来，RNA二级结构的算法预测一直是一个活跃的研究领域。尽管从那时起有了许多创新，但我们最好的技术仍不完美。RNA二级结构预测引擎的主要方法是1981年由祖克（Zuker）和施蒂格勒（Stiegler）首次描述的递归算法。这些算法有一些众所周知的局限性；一个明显的缺陷是对多环（也称为螺旋连接）的临时处理，这种情况至今仍然存在。虽然已经提出了几种用于多环的先进模型，但似乎有人认为将它们纳入递归算法会导致计算难题，因此不存在针对这些模型的算法。其中一些模型包括基于雅各布森 - 斯托克迈耶（Jacobson-Stockmayer）聚合物理论的经典模型，以及另一个由阿尔伯茨（Aalberts）和纳达戈帕尔（Nadagopal）提出的纳入双长度尺度聚合物物理学的模型。我们已经为这些模型中的每一个实现了实用且易于处理的算法。然而，在实现这些算法后，我们发现没有一个先进模型比用于多环的原始临时模型更好。虽然这出乎意料，但它支持了当前模型的实践。
