The Tail of the Telomere

The structure of a higher-order G-quadruplex structure for human telomeric DNA is presented. The structure was determined by a novel integrated approach in which molecular dynamics simulations were used to produce a stable structure, from which specific experimentally accessible properties were predicted. These properties were tested by sedimentation velocity and steady-state fluorescence measurements. The structure that emerges is a dimeric structure with two quadruplex units, each with a different structure. The interface between the quadruplex units is stabilized by specific stacking interactions of loop nucleotides. The interface is a unique structure and a unique target for drug design.