Modeling context-dependent conformation parameters of DNA duplexes

Abstract

The context-dependent conformation preference and the conformational lability of DNA play important roles in the formation of complexes with various proteins including transcription factors, regulatory and nucleosomal proteins. The extraction of context-dependent DNA helix parameters and the related deformation characteristics from static crystalline DNA duplex structures involves artifacts caused by the crystal packing effects. A series of 150 tetradeca-and pentadecameric DNA duplexes with various sequences occurring in aqueous solution under physiological conditions have been simulated by the method of molecular dynamics (MD). The context-dependent conformation parameters of XY dinucleotides were determined from analysis of the MD trajectories of equilibrium thermal fluctuations of 3D structures for a large set of 14-membered DNA duplexes in aqueous solution. The mean values of the helix parameters roll and twist as well as their thermal fluctuations for the TA, TG, and CG pair steps proved to take special values significantly differing from the averages over all pairs. This fact suggests that DNA sites rich in TA, TG, and CG are capable of forming special local equilibrium structures and have increased conformational plasticity, thus favoring conformational matching at the sites of regulatory and nucleosomal protein binding.