Sequence dependent free energy profiles of localized B- to A-form transition of DNA in water

Abstract

DNA carries an inherent polymorphism, which surfaces under various external conditions. While B-form remains predominant under normal physiological conditions for most of the DNA sequences, low humidity and increased ion concentration cause B- to A-form transition. Certain proteins and molecules also sometimes cause local deformation of the DNA to the specific A-form. Previous experimental and computational studies focused on the overall B- to A-form transition. Here for the first time we investigated thermodynamics and mechanism of B- to A-form transition in water for various DNA sequences at a local dinucleotide base pair level. We introduced a new reaction coordinate Zp′, based on the unique order parameter Zp, to drive B- to A-form transition locally and thereby calculate free energy profiles for the same for all the ten different dinucleotide steps embedded in a twelve base pair DNA. Results show that the trend of “A” and “B” philicity observed in experiment is preserved even at this local dinucleotide level, indicating its localized origin. Higher free energy cost obtained here is attributed to the cost of creating B/A junctions along with formation of B->A transition at dimer level. We find that while water energetically stabilizes A-form for all the ten different dinucleotide steps to various extents, entropy acts against it. Therefore, we find that the stability of B-form DNA in water is entropic in origin. Mechanism of the conversion appears to be triggered by Slide; however, backbone parameters change concertedly.