Comparative RNA structure prediction beyond stochastic context free grammars

RNA分子是任何细胞中许多基本过程的核心。它们对在细胞中合成的一组蛋白质的信息进行编码；它们帮助合成蛋白质；它们控制蛋白质的生产率(见2006年诺贝尔医学奖)；它们本身也充当基因(所谓的RNA基因)。其中许多功能依赖于RNA分子的结构。RNA分子是由四个基本构件组成的长度可变的线性链，核苷酸表示为A、C、G和U。RNA结构由RNA序列中不连续的核苷酸对之间的弱氢键定义；三个可能的对是{A，U}，{G，C}和{G，U}。RNA序列可以采用的可能的RNA结构的数量随着序列的长度呈指数增长。理论科学家面临的挑战是挑选出赋予RNA分子功能性质的RNA结构。为了解决这一挑战，现有的大多数方法都依赖于假设RNA分子具有最稳定的结构。最近的结果表明，这一假设并不普遍成立。我们建议开发新的、显著改进的理论方法，这些方法不依赖于这一假设，并且克服了现有方法的主要概念限制，以便改进RNA结构预测、RNA基因预测，并解决当今分子生物学中许多最基本和最令人兴奋的问题。

RNA molecules are at the core of numerous fundamental processes in any cell. They encode information on the set of proteins to be synthesized in a cell; they help synthesize proteins; they control protein-production rates (see Nobel Prize in Medicine 2006); and they also act as genes in their own right (so-called RNA genes). Many of these functions rely on the structure of the RNA molecule.RNA molecules are linear chains of variable lengths made of four elementary building blocks, the nucleotides denoted A, C, G and U. An RNA structure is defined by weak hydrogen bonds between pairs of non-consecutive nucleotides in the RNA sequence; the three possible pairs are {A, U}, {G, C} and {G, U}. The number of possible RNA structures that an RNA sequence can assume grows exponentially with the length of the sequence. The challenge to the theoretical scientist is to single out the RNA structure that confers the functional property to the RNA molecule.To address this challenge, most existing methods rely on the assumption that RNA molecules assume the most stable structure. Recent results show that this assumption does not hold in general. We propose to develop novel,significantly improved, theoretical methods which do not rely on this assumption and which overcome the major conceptual limitations of the existing methods in order to improve RNA structure prediction, RNA gene prediction and to address many of the most fundamental and exciting questions in molecular biology today.