Absolute binding-free energies between standard RNA/DNA nucleobases and amino-acid sidechain analogs in different environments

Nucleic Acids Research
Anita de Ruiter, Bojan Zagrovic


Despite the great importance of nucleic acid-protein interactions in the cell, our understanding of their physico-chemical basis remains incomplete. In order to address this challenge, we have for the first time determined potentials of mean force and the associated absolute binding free energies between all standard RNA/DNA nucleobases and amino-acid sidechain analogs in high- and low-dielectric environments using molecular dynamics simulations and umbrella sampling. A comparison against a limited set of available experimental values for analogous systems attests to the quality of the computational approach and the force field used. Overall, our analysis provides a microscopic picture behind nucleobase/sidechain interaction preferences and creates a unified framework for understanding and sculpting nucleic acid-protein interactions in different contexts. Here, we use this framework to demonstrate a strong relationship between nucleobase density profiles of mRNAs and nucleobase affinity profiles of their cognate proteins and critically analyze a recent hypothesis that the two may be capable of direct, complementary interactions.


May 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·J T Wong
Nov 1, 1991·Journal of Molecular Evolution·D Haig, L D Hurst
Oct 1, 1973·Die Naturwissenschaften·C R Woese
Dec 1, 1968·Journal of Molecular Biology·F H Crick
Apr 1, 1966·Proceedings of the National Academy of Sciences of the United States of America·C R WoeseS A Dugre
Aug 7, 1993·Journal of Theoretical Biology·N C Kyrpides, C A Ouzounis
Oct 1, 1995·Biophysical Journal·L YangB M Pettitt
Feb 4, 1998·Biophysical Journal·J Norberg, L Nilsson
Jul 17, 1998·Journal of Molecular Evolution·M Yarus
Mar 31, 2000·Molecular Biology and Evolution·S J FreelandL D Hurst
Jul 27, 2001·Journal of Molecular Biology·J Allers, Y Shamoo
May 23, 2002·Journal of the American Chemical Society·Riccardo ChelliVincenzo Schettino
Aug 9, 2002·The Journal of Biological Chemistry·Christophe BiotMarianne Rooman
Mar 26, 2003·Journal of Molecular Biology·Alan C ChengAlan D Frankel
May 1, 1964·Biochemistry·E O AKINRIMISI, P O TSO
Nov 13, 2003·Journal of the American Chemical Society·Christophe BiotMarianne Rooman
Dec 19, 2003·Nucleic Acids Research·Michael M HoffmanAndrew D Ellington
Jan 15, 2004·Journal of the American Chemical Society·Alan C Cheng, Alan D Frankel
Jul 21, 2004·Journal of Computational Chemistry·Chris OostenbrinkWilfred F van Gunsteren
Sep 29, 2006·The Journal of Physical Chemistry. B·Lesley R RutledgeStacey D Wetmore
Jan 2, 2009·IUBMB Life·Eugene V Koonin, Artem S Novozhilov
Jun 11, 2009·The Journal of Physical Chemistry. B·Gerhard König, Stefan Boresch
Oct 2, 2009·Journal of Molecular Evolution·Michael YarusRob Knight
Apr 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·David B F Johnson, Lei Wang
Feb 24, 2011·Biology Direct·Andrei S RodinSergei N Rodin
Jun 9, 2011·The Journal of Physical Chemistry. a·Lesley R RutledgeStacey D Wetmore
Aug 20, 2011·BMC Bioinformatics·Irina Tuszynska, Janusz M Bujnicki
Jul 23, 2013·Nucleic Acids Research·Anton A Polyansky, Bojan Zagrovic
Oct 9, 2012·Journal of Chemical Theory and Computation·Maria M ReifChris Oostenbrink

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