Rodriguez Anabel, Wright Gabriel, Emrich Scott, Clark Patricia L
Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, Indiana, 46556.
Department of Computer Science & Engineering, University of Notre Dame, Notre Dame, Indiana, 46556.
Protein Sci. 2018 Jan;27(1):356-362. doi: 10.1002/pro.3336. Epub 2017 Nov 21.
Most amino acids can be encoded by more than one synonymous codon, but these are rarely used with equal frequency. In many coding sequences the usage patterns of rare versus common synonymous codons is nonrandom and under selection. Moreover, synonymous substitutions that alter these patterns can have a substantial impact on the folding efficiency of the encoded protein. This has ignited broad interest in exploring synonymous codon usage patterns. For many protein chemists, biophysicists and structural biologists, the primary motivation for codon analysis is identifying and preserving usage patterns most likely to impact high-yield production of functional proteins. Here we describe the core functions and new features of %MinMax, a codon usage calculator freely available as a web-based portal and downloadable script (http://www.codons.org). %MinMax evaluates the relative usage frequencies of the synonymous codons used to encode a protein sequence of interest and compares these results to a rigorous null model. Crucially, for analyzing codon usage in common host organisms %MinMax requires only the coding sequence as input; with a user-input codon frequency table, %MinMax can be used to evaluate synonymous codon usage patterns for any coding sequence from any fully sequenced genome. %MinMax makes no assumptions regarding the impact of transfer ribonucleic acid concentrations or other molecular-level interactions on translation rates, yet its output is sufficient to predict the effects of synonymous codon substitutions on cotranslational folding mechanisms. A simple calculation included within %MinMax can be used to harmonize codon usage frequencies for heterologous gene expression.
大多数氨基酸都可以由多个同义密码子编码，但这些密码子的使用频率很少相等。在许多编码序列中，稀有同义密码子与常见同义密码子的使用模式是非随机的，且处于选择之下。此外，改变这些模式的同义替换可能会对编码蛋白质的折叠效率产生重大影响。这引发了人们对探索同义密码子使用模式的广泛兴趣。对于许多蛋白质化学家、生物物理学家和结构生物学家来说，密码子分析的主要动机是识别和保留最有可能影响功能性蛋白质高产的使用模式。在这里，我们描述了%MinMax的核心功能和新特性，%MinMax是一个密码子使用计算器，可作为基于网络的门户免费获取，并可下载脚本（http://www.codons.org）。%MinMax评估用于编码感兴趣蛋白质序列的同义密码子的相对使用频率，并将这些结果与严格的零模型进行比较。至关重要的是，为了分析常见宿主生物体中的密码子使用情况，%MinMax只需要编码序列作为输入；通过用户输入的密码子频率表，%MinMax可用于评估来自任何全测序基因组的任何编码序列的同义密码子使用模式。%MinMax对转运核糖核酸浓度或其他分子水平相互作用对翻译速率的影响不做任何假设，但其输出足以预测同义密码子替换对共翻译折叠机制的影响。%MinMax中包含的一个简单计算可用于协调异源基因表达的密码子使用频率。
