SUNY at Albany
June 19-23, 2001
All coordination sites in the central channel of G-quadruplexes need not be occupied by cations: A 6-nanosecond molecular dynamics study
Guanine tetrads are formed spontaneously by guanine rich sequences in the presence of certain cations. Various quadruplex helical structures, stabilized by such tetrads, apparently play an important biological role in vivo. To understand the importance of the cations a six nanosecond molecular dynamics simulation has been performed on a 7-mer G- quadruplex, surrounded by Na+ counter ions and explicit water molecules. The quadruplex structure is maintained during the entire simulation, but undergoes interesting structural changes, which enable the solvent molecules to enter the empty central channel of the initial structure. This channel is fully hydrated within the first 100 ps and the quadruplex retains its structural characteristics in the absence of any coordinated ions. Two ions move into the central channel between 0.5 to 2 ns of MD simulation, by replacing some of the water molecules. The ions once trapped within the quadruplex channel are not expelled even during 1.5 ns of MD at 400K. In fact they penetrate deeper into the channel to facilitate entry of additional ions, though all coordination sites within the quadruplex are not occupied even after 6.1 ns of MD simulation. The small conformational changes accompanying the entry of cations into the central channel lead to more favourable free energy of hydration for the quadruplex structure.
Shibasish Chowdhury and Manju Bansal
Molecular Biophysics Unit, Indian Institute of Science, Bangalore-560012, India,