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Ions surround nucleic acids in what is referred to as an ion atmosphere. As a result, the folding and dynamics of RNA and DNA and their complexes with proteins and with each other cannot be understood without a reasonably sophisticated appreciation of these ions' electrostatic interactions. However, the underlying behavior of the ion atmosphere follows physical rules that are distinct from the rules of site binding that biochemists are most familiar and comfortable with. The main goal of this review is to familiarize nucleic acid experimentalists with the physical concepts that underlie nucleic acid-ion interactions. Throughout, we provide practical strategies for interpreting and analyzing nucleic acid experiments that avoid pitfalls from oversimplified or incorrect models. We briefly review the status of theories that predict or simulate nucleic acid-ion interactions and experiments that test these theories. Finally, we describe opportunities for going beyond phenomenological fits to a next-generation, truly predictive understanding of nucleic acid-ion interactions. [ABSTRACT FROM AUTHOR]

Advances in our understanding of macromolecular structure come from experimental methods, such as X-ray crystallography, and also computational analysis of the growing number of atomic models obtained from such experiments. The later analyses have made it possible to develop powerful tools for structure prediction and optimization in the absence of experimental data. In recent years, a synergy between these computational methods for crystallographic structure determination and structure prediction and optimization has begun to be exploited. We review some of the advances in the algorithms used for crystallographic structure determination in the Phenix and Crystallography & NMR System software packages and describe how methods from ab initio structure prediction and refinement in Rosetta have been applied to challenging crystallographic problems. The prospects for future improvement of these methods are discussed. [ABSTRACT FROM AUTHOR]

Advances over the past few years have begun to enable prediction and design of macromolecular structures at near-atomic accuracy. Progress has stemmed from the development of reasonably accurate and efficiently computed all-atom potential functions as well as effective conformational sampling strategies appropriate for searching a highly rugged energy landscape, both driven by feedback from structure prediction and design tests. A unified energetic and kinematic framework in the Rosetta program allows a wide range of molecular modeling problems, from fibril structure prediction to RNA folding to the design of new protein interfaces, to be readily investigated and highlights areas for improvement. The methodology enables the creation of novel molecules with useful functions and holds promise for accelerating experimental structural inference. Emerging connections to crystallographic phasing, NMR modeling, and lower-resolution approaches are described and critically assessed. [ABSTRACT FROM AUTHOR]