Charge Transport through Methylated DNA Strand
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Charge Transport through Methylated DNA Strand Jianqing Qi, and M. P. Anantram Department of Electrical Engineering, University of Washington, Seattle, WA 98195, USA
ABSTRACT Charge transport through an eight-base pair methylated DNA strand and its native counterpart have been investigated. We focus on three factors, contact coupling, decoherence and temperature, which can contribute to DNA charge transport. Our results show that with the same choice of contact coupling, in the phase-coherent limit the transmission of the methylated strand is smaller in the bandgap at energies close to the highest occupied molecular orbital (HOMO), while inside the HOMO band, the transmission is oscillatory and the methylated DNA may have a larger transmission in certain energy windows. The trend in transmission also holds in the presence of the decoherence though there is a crossover in the transmission of the native and methylated strands away from the HOMO level. We also find that the transport depends on the strength of contact coupling and the measurement temperature.
INTRODUCTION Methylation of cytosine involves the replacement of the hydrogen atom at the 5th position of the cytosine pyrimidine by a methyl group [1]. Cytosine methylation in DNA is known to play a crucial role in many biological processes, such as the regulation of gene expression, X chromosome inactivation, cellular differentiation, embryonic development and genomic imprinting [2,3]. The abnormal behaviors of DNA methylation are also responsible for diseases including cancer [4]. Targeting and identifying methylated DNA is therefore important for disease diagnosis and drug design. Current detection techniques involve chemical modification [5], which may not be trustworthy in distinguishing small changes during the amplification processes. Recently, new techniques using the electrical properties of DNA bases have been used to detect methylated bases [6,7]. The results show that the methylated sequence/base can be identified with direct conductance measurement. In addition to single-molecule electrical approach, electrochemical methods have also been used to detect methylated DNA [8, 9]. Despite the progress in experiment, understanding of charge transport through a methylated DNA strand/base from a theoretical perspective is lacking. In this work, we study charge transport through an 8 base-pair methylated DNA strand and its native counterpart used in reference [7]. We aim to provide understanding of the effect of cytosine methylation on charge transport through DNA strand under various measurement environments. THEORY We focus on the two DNA sequences used in reference [7]: 1) 5’-GCGCGCGC-3’ (GC8); 2) the methylated counterpart, 5’-GCmGCmGCmGCm-3’ (GCm8). The native B-form
DNA structure is generated by Nucleic Acid Builder [10]. The backbone is deleted and the nitrogenous bases are terminated with hydrogen atoms. For the methylated DNA, a methyl group is added to the 5th position of the pyrimidine and then relaxed at B3LYP/6-31G (d) level using Gaussian 09
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