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Electrostatics Explains the Position‐Dependent Effect of G⋅U Wobble Base Pairs on the Affinity of RNA Kissing Complexes
Author(s) -
AbiGhanem Josephine,
Rabin Clémence,
Porrini Massimiliano,
Dausse Eric,
Toulmé JeanJacques,
Gabelica Valérie
Publication year - 2017
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.201700337
Subject(s) - base pair , speed wobble , electrostatics , rna , wobble base pair , chemistry , loop (graph theory) , chemical physics , position (finance) , molecular dynamics , static electricity , physics , crystallography , computational chemistry , dna , quantum mechanics , transfer rna , biochemistry , mathematics , combinatorics , gene , finance , economics
In the RNA realm, non‐Watson–Crick base pairs are abundant and can affect both the RNA 3D structure and its function. Here, we investigated the formation of RNA kissing complexes in which the loop–loop interaction is modulated by non‐Watson–Crick pairs. Mass spectrometry, surface plasmon resonance, and UV‐melting experiments show that the G⋅U wobble base pair favors kissing complex formation only when placed at specific positions. We tried to rationalize this effect by molecular modeling, including molecular mechanics Poisson–Boltzmann surface area (MMPBSA) thermodynamics calculations and PBSA calculations of the electrostatic potential surfaces. Modeling reveals that the G⋅U stabilization is due to a specific electrostatic environment defined by the base pairs of the entire loop–loop region. The loop is not symmetric, and therefore the identity and position of each base pair matters. Predicting and visualizing the electrostatic environment created by a given sequence can help to design specific kissing complexes with high affinity, for potential therapeutic, nanotechnology or analytical applications.