UNASSIGNED: The telomeric G-quadruplexes for their unique structural features are considered as potential anticancer drug targets. These, however, exhibit structural polymorphism as different topology types for the intra-molecular G-quadruplexes from @entity1 telomeric G-rich sequences have been reported based on NMR spectroscopy and X-ray crystallography. These techniques provide detailed atomic-level information about the molecule but relative conformational stability of the different topologies remains unsolved. Therefore, to understand the conformational preference, we have carried out quantum chemical calculations on G-quartets; used all-atom @entity74 ( @entity74 ) simulations and @entity74 ( @entity74 ) simulations to characterize the four @entity1 telomeric G-quadruplex topologies based on its G-tetrad core-types, viz., parallel, anti-parallel, mixed-(3   +   1)-form1 and mixed-(3   +   1)-form2. We have also studied a non-telomeric sequence along with these telomeric forms giving a comparison between the two G-rich forms. The structural properties such as base pairing, stacking geometry and backbone conformations have been analyzed. The quantum calculations indicate that presence of a @entity1372 ion inside the G-tetrad plane or two @entity972 ions on both sides of the plane give it an overall planarity which is much needed for good stacking to form a helix. Molecular dynamics simulations indicate that capping of the G-tetrad core by the TTA loops keep the terminal @entity2774 bases away from water. The @entity74 simulations along with equilibrium @entity74 studies indicate that the parallel and non-telomeric forms are comparatively less stable. We could come to the conclusion that the anti-parallel form and also the mixed-(3   +   1)-form1 topology are most likely to represent the major conformation. This article is protected by copyright. All rights reserved.

A comparison of four different conformations adopted by XXXX telomeric G-Quadruplex using Computer Simulations.

@entity1 :: ('9606', 'Species') :: ['human'] @entity1372 :: ('MESH:D012964', 'Chemical') :: ['sodium'] @entity2774 :: ('MESH:D006147', 'Chemical') :: ['guanine'] @entity74 :: ('MESH:D030342', 'Disease') :: ['Steered Molecular Dynamics', 'Molecular Dynamics', 'SMD', 'MD'] @entity972 :: ('MESH:D011188', 'Chemical') :: ['potassium']
@entity1 :: (9606,Species) :: ['human']
