title: Absolute binding-free energies between standard RNA/DNA nucleobases and amino-acid sidechain analogs in different environments.
abstract: 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.
authors.affiliation: Department of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, Vienna 1030, Austria.
authors.forename: Anita
authors.initials: A
authors.lastname: de Ruiter
authors.affiliation: Department of Structural and Computational Biology, Max F. Perutz Laboratories, University of Vienna, Vienna 1030, Austria bojan.zagrovic@univie.ac.at.
authors.forename: Bojan
authors.initials: B
authors.lastname: Zagrovic
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D005815:Genetic Code; D000432:Methanol / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D012313:RNA / Q000737:chemistry*; D012333:RNA, Messenger / Q000737:chemistry; D016601:RNA-Binding Proteins / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D000596:Amino Acids; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014867:Water; D012313:RNA; D004247:DNA; D000432:Methanol