DNA quadruplex folding formalism - A tutorial on quadruplex topologies

Quadruplexes of DNA adopt a large variety of topologies that are dependent on their environment. We have been developing a formalism for quadruplex folding based on the relationship between base and its sugar - as defined by the glycosidic bond angle. By reducing the quadruplex stem to a description based on two finite states of the range of angles the glycosidic bond angle may adopt, the description of the relationships of type of loop and groove widths of a quadruplex stem are possible. In its current form this formalism has allowed for the prediction of some unimolecular quadruplex topologies. Its rules, whilst developed for unimolecular quadruplexes of three loops, are of general utility in understanding the interdependency of structural characteristics of multimolecular folds, as well as unimolecular quadruplexes of more than three loops. Here we describe current understanding of the interdependent structural features that define the quadruplex fold, and provide a tutorial for the use and application of this formalism. (C) 2013 Elsevier Inc. All rights reserved.