Structural, dynamical and catalytic interplay between Mg2+ ions and RNA. Vices and virtues of atomistic simulations

Mg2+ ions are essential for RNA biology as they allow RNA filaments to assume their natively folded structure and promote their function in a variety of biological processes. The Mg2+ positive charge screens the negative one of the phosphate backbone, permitting RNAs to assume compact tertiary structures. Moreover, key biological processes, such as formation of mature messenger RNA or transfer RNA, are promoted by catalytic Mg2+-dependent RNA enzymes. Mg2+ ions regulate this very broad range of functions by interacting non-specifically and/or specifically (either directly or via water-mediated contacts) with RNA in several possible binding architectures. Despite being Mg2+ an alkaline earth ion and binding to RNA without forming coordination bonds, its unique interplay with RNA is ascribable to the large charge transfer and polarization effects exerted on the polynucleotide chain. This key feature makes difficult a correct description of we interactions with simple empirical force field models, requiring the use of ab initio or multiscale methods. In this review we provide a survey of strengths and limitations of different atomistic simulation techniques, ranging from force field-based molecular dynamics to oh initio and hybrid quantum-classical (QM/MM) methods, in the structural and functional description of Mg2+-RNA binding, showing how in silico studies have contributed to reveal important aspects of RNA biology. Computational perspectives in this field are finally given. (C) 2016 Elsevier B.V. All rights reserved.