Topological Constraints and Their Conformational Entropic Penalties on RNA Folds.

Abstract:

:Functional RNAs can fold into intricate structures using a number of different secondary and tertiary structural motifs. Many factors contribute to the overall free energy of the target fold. This study aims at quantifying the entropic costs coming from the loss of conformational freedom when the sugar-phosphate backbone is subjected to constraints imposed by secondary and tertiary contacts. Motivated by insights from topology theory, we design a diagrammatic scheme to represent different types of RNA structures so that constraints associated with a folded structure may be segregated into mutually independent subsets, enabling the total conformational entropy loss to be easily calculated as a sum of independent terms. We used high-throughput Monte Carlo simulations to simulate large ensembles of single-stranded RNA sequences in solution to validate the assumptions behind our diagrammatic scheme, examining the entropic costs for hairpin initiation and formation of many multiway junctions. Our diagrammatic scheme aids in the factorization of secondary/tertiary constraints into distinct topological classes and facilitates the discovery of interrelationships among multiple constraints on RNA folds. This perspective, which to our knowledge is novel, leads to useful insights into the inner workings of some functional RNA sequences, demonstrating how they might operate by transforming their structures among different topological classes.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Mak CH,Phan ENH

doi

10.1016/j.bpj.2018.03.035

subject

Has Abstract

pub_date

2018-05-08 00:00:00

pages

2059-2071

issue

9

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(18)30452-1

journal_volume

114

pub_type

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