Poster Presenter

Structural Studying of Two-Module Thrombin Binding Dna Aptamers
Alexei Kopylov, Andrey Golovin, Roman Reshetnikov, Timur Turchaninov, Alina Yuminova,Vera Spiridonova, Alexander Arutyunyan
Russia

Molecular dynamics simulation (MD) using super-computer clusters has been applied to explore structural details of derivatives of thrombin-binding DNA aptamer (TBA) having G-quadruplex structural module. Two different models of conventional 15-mer TBA (15-TBA) which were based on the controversial NMR and X-ray data were considered: they are distinguished by several key features, mainly by the chain polarity. MD comparison of these models revealed that NMR model has more definite structure. Taking G-quadruplex as one structural module, another double-strained module has been computer added to 15-TBA to create a model of two-modular 31-mer TBA (31-TBA). Variants of 31-TBA models have been simulated; each consists of two modules connected by flexible hinge region. G-quadruplex module is able to stabilize neighboring module structures which has very low melting temperature. Comparative temperature stability of G-quadruplex structures have been studied by circular dichroism spectra. G-quadruplex structure is a target, as well as a part of different kind of potential drugs, therefore this study is applied for rational drug design for the thrombin inhibitors. Microfluidic chip capillary electrophoresis data on aptamers affinity to human thrombin are also presented. The work has been supported by Rosnauka 02.512.11.2242.1-08; RFBR 08-04-01244a.