Statistical mechanics of RNA folding: importance of alphabet size

TL;DR

This paper presents a minimalist model to study how the size of the nucleotide alphabet affects RNA folding, revealing significant differences in stability and configuration diversity between two-letter and four or six-letter alphabets.

Contribution

It introduces a simplified model that highlights the impact of alphabet size on RNA secondary-structure formation and stability, emphasizing qualitative differences between two-letter and larger alphabets.

Findings

Two-letter alphabets have many alternative folding configurations.

Four or six-letter alphabets lead to fewer competing structures.

Sequences with four or more bases have more stable ground states.

Abstract

We construct a minimalist model of RNA secondary-structure formation and use it to study the mapping from sequence to structure. There are strong, qualitative differences between two-letter and four or six-letter alphabets. With only two kinds of bases, there are many alternate folding configurations, yielding thermodynamically stable ground-states only for a small set of structures of high designability, i.e., total number of associated sequences. In contrast, sequences made from four bases, as found in nature, or six bases have far fewer competing folding configurations, resulting in a much greater average stability of the ground state.