Minimum sequence requirements for selective RNA-ligand binding: A molecular mechanics algorithm using molecular dynamics and free-energy techniques
Minimum sequence requirements for selective RNA-ligand binding: A molecular mechanics algorithm using molecular dynamics and free-energy techniques
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DOI：
10.1002/jcc.20459
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发表时间：
2006-11-15
影响因子：
3
通讯作者：
Mecozzi, Sandro
中科院分区：
文献类型：
--
作者：
Anderson, Peter C.;Mecozzi, Sandro
体外进化技术允许开发具有独特功能的RNA分子。然而，这些技术并不一定能识别出最简单的RNA结构来执行其功能。确定与特定配体结合的最简单的RNA目前仅限于实验方案。给你，我们介绍了一种基于分子力学的算法，采用分子动力学模拟和自由能方法来预测选择性配体结合RNA的最小序列要求。该算法涉及从实验确定的RNA-配体复合物结构中迭代删除核苷酸，对每个截短结构进行能量最小化和分子动力学，并评估哪些截短不会阻止RNA与配体结合。该算法允许预测序列修饰对RNA结构稳定性和配体结合能的影响。我们已经在AMBER程序套件中实现了该算法，但它可以在任何核酸参数化的分子力学力场中实现。测试案例显示的实用性和准确性的方法。(C)2006 Wiley Periodicals，Inc.
In vitro evolution techniques allow RNA molecules with unique functions to be developed. However, these techniques do not necessarily identify the simplest RNA structures for performing their functions. Determining the simplest RNA that binds to a particular ligand is currently limited to experimental protocols. Here., we introduce a molecular-mechanics based algorithm employing molecular dynamics simulations and free-energy methods to predict the minimum sequence requirements for selective ligand binding to RNA. The algorithm involves iteratively deleting nucleotides from an experimentally determined structure of an RNA-ligand complex, performing energy minimizations and molecular dynamics on each truncated structure, and assessing which truncations do not prohibit RNA binding to the ligand. The algorithm allows prediction of the effects of sequence modifications on RNA structural stability and ligand-binding energy. We have implemented the algorithm in the AMBER suite of programs, but it could be implemented in any molecular mechanics force field parameterized for nucleic acids. Test cases are presented to show the utility and accuracy of the methodology. (C) 2006 Wiley Periodicals, Inc.