A Method to Predict the Structure and Stability of RNA/RNA Complexes

Abstract

Summary RNA/RNA interactions are essential for genomic RNA dimerization and regulation of gene expression. Intermolecular loop-loop base pairing is a widespread and functionally important tertiary structure motif in RNA machinery. However, computational prediction of intermolecular loop-loop base pairing is challenged by the entropy and free energy calculation due to the conformational constraint and the intermolecular interactions. In this chapter, we describe a recently developed statistical mechanics-based method for the prediction of RNA/RNA complex structures and stabilities. The method is based on the virtual bond RNA folding model (Vfold). The main emphasis in the method is placed on the evaluation of the entropy and free energy for the loops, especially tertiary kissing loops. The method also uses recursive partition function calculations and two-step screening algorithm for large, complicated structures of RNA/RNA complexes. As case studies, we use the HIV-1 Mal dimer and the siRNA/HIV-1 mutant (T4) to illustrate the method.

Modeling Loop Composition and Ion Concentration Effects in RNA Hairpin Folding Stability

“…In general, the folding of RNA is thought to be hierarchical (38)(39)(40), and the secondary structure (two-dimensional (2D)) is more stable than tertiary folding (12,41). Thus, the thermodynamic stability of RNA structure can be largely determined at the 2D level by free-energy approaches such as Mfold (42)(43)(44), RNAstructure (45)(46)(47), RNAfold (48)(49)(50), and Vfold (51)(52)(53)(54)(55)(56)(57)(58) based on nearest-neighbor thermodynamic free-energy parameters measured at 1 M NaCl (59)(60)(61). However, most cellular activities involving RNA molecules are not in 1 M NaCl, and a typical ionic environment in mammalian cells contains a mixture of monovalent (such as Na þ and K þ ) and multivalent ions (such as Mg 2þ ) (62).…”

In silico Design of Linear DNA for Robust Cell-Free Gene Expression

“…These REP sequences were all selected from RNAstem database 1 . Vfold2D webserver ( Cao and Chen, 2005 , 2009 ; Xu et al, 2014 ; Xu and Chen, 2016 ) was used to predict the secondary structure of the designed mRNA sequences, and 3dRNA v2.0 webserver ( Wang et al, 2015 , 2017 , 2019 ) was used to construct the 3D structure of mRNA. At last, HDOCK SERVER was still used to simulate and evaluate the docking status between mRNA and RNase II.…”

“…This study used Vfold2D (version2.0): Predicting RNA 2D structures webserver ( Cao and Chen, 2005 , 2009 ; Xu et al, 2014 ; Xu and Chen, 2016 ) 3 to predict the secondary structure of RNA.…”

An NMR-based approach reveals the core structure of the functional domain of SINEUP lncRNAs

“…For RNAstructure, we selected a maximum loop size of 30, maximum % energy difference of 10, maximum number of structures 20, window size 3, gamma 1, iteration of 1 and minimum helix length of 3 were selected ( 34 ). For Vfold2D, Turner parameters (04 version) were selected ( 35 ). For Vsfold5, the polymer model options were ‘Jacobson-Stockmayer’, ‘Kuhn-length 9’ (a typical value for functional RNAs), ‘search for pseudo-knots’, a minimum linkage stem length of 5, a leading edge length of 7 and no inclusion of Mg++ ( 36 ).…”