A toolbox for predicting g-quadruplex formation and stability

Abstract

G-quadruplexes are four stranded nucleic acid structures formed around a core of guanines, arranged in squares with mutual hydrogen bonding. Many of these structures are highly thermally stable, especially in the presence of monovalent cations, such as those found under physiological conditions. Understanding of their physiological roles is expanding rapidly, and they have been implicated in regulating gene transcription and translation among other functions. We have built a community-focused website to act as a repository for the information that is now being developed. At its core, this site has a detailed database (QuadDB) of predicted G-quadruplexes in the human and other genomes, together with the predictive algorithm used to identify them. We also provide a QuadPredict server, which predicts thermal stability and acts as a repository for experimental data from all researchers. There are also a number of other data sources with computational predictions. We anticipate that the wide availability of this information will be of use both to researchers already active in this exciting field and to those who wish to investigate a particular gene hypothesis.

Figure 1

Annual publication rate in the G-quadruplex field in the past decade. Data obtained from the Web of Knowledge, searching for the term “G-quadruplex” or “G-tetraplex.” The solid line is an exponential fit to the data.

Figure 2

Sample output from the data search component of Quadbase. The search query is shown at the bottom of the figure.

Figure 3

Sample predictions from QuadPredict, using Bayesian inference to calculate predicted melting temperatures together with predicted uncertainties.