The Electronic Behavior of Zinc-Finger Protein Binding Sites in the Context of the DNA Extended Ladder Model

Abstract

Instead of ATCG letter alignments, typically used in bioinformatics, we propose a new alignment method using the probability distribution function of the bottom of the occupied molecular orbital (BOMO), highest occupied molecular orbital (HOMO), and lowest unoccupied orbital (LUMO). We apply the technique to transcription factors with Cys 2 His 2 zinc fingers. These transcription factors search for binding sites, probing for the electronic patterns at the minor and major DNA groves. The eukaryotic Cys 2 His 2 zinc finger proteins bind to DNA ubiquitously at highly conserved domains. They are responsible for gene regulation and the spatial organization of DNA. To study and understand these zinc finger DNA-protein interactions, we use the extended ladder in the DNA model proposed by Zhu et al. [1]. Considering one single spinless electron in each nucleotide π -orbital along a double DNA chain (dDNA), we find a typical pattern for the bottom of BOMO, HOMO, and LUMO along the binding sites. We specifically looked at two members of zinc finger protein family: specificity protein 1 (SP1) and early grown response 1 transcription factors (EGR1). When the valence band is filled, we find electrons in the purines along the nucleotide sequence, compatible with the electric charges of the binding amino acids in SP1 and EGR1 zinc finger.

Superstructure Detection in Nucleosome Distribution Shows Common Pattern within a Chromosome and within the Genome

“…For instance, a typical nucleosome distribution around TSSs indicates nucleosome depletion, resulting in a nucleosome-free region (NFR) whereas the nucleosomes downstream of TSS are equally spaced (20). A similar observation around CTCF is obtained: An array of well-positioned nucleosomes flank the sites occupied by the insulator binding protein CTCF across the human genome (21). Despite the efforts, the global picture of nucleosome positioning remains elusive until a recent study that has reported three types of nucleosomal arrangement by analyzing the nucleosome spacing and phasing in a genome (22).…”

Prediction and comparative analysis of CTCF binding sites based on a first principle approach

“…Electrons can easily hop for 16.8 (AT rich sequences) or 25 Å (CG rich) [20], which comprehend at least 5 to 8 bp of the surrounding nucleotides over the core 20-mer binding site. Results with transcription factor specificity protein 1 (SP1) and early growth response protein 1 (EGR1) [10] show the existence of HOMO and LUMO surrounding binding site. Similar phenomena happen for CTCF as we will report in this work, although the biological function of HOMO and LUMO is unknown yet.…”

“…In this paper we present a new method to finding CTCF binding sites based on the interaction of the zinc finger and the electronic cloud of the nucleotide π-orbital of the double DNA (dDNA). This is a first principle approach method, because we compute the local electron density of states using electron-nucleotide interactions along the genome [10] (referee 1: item 5). This quantum mechanic charge transport description of the nucleotide, typical in semiconductor physics, adds a new layer of information beyond traditional four letter nucleotide genomics.…”

“…First of all, we collect 23 experimentally detected CTCF-DNA binding site (see supplementary material S1 (https://stacks.iop.org/PB/19/036005/mmedia)). Then, we study the electronic cloud of the nucleotide π-orbital using [10]. This analysis extends the usual nucleotide alignment based on hydrogen bonds, adding information about the electronic behavior in CTCF binding sites as ground state, highest occupied orbital (HOMO) and lowest unoccupied orbital (LUMO) (see S2).…”

An asymmetric mesoscopic model for single bulges in RNA

“…The PB model is under active development and is applied to a number of different physical situations involving oligonucleotides. Some recent examples for DNA are its use to study bubble length distribution, 34 charge transport 35,36 over-stretching transition, 37 and flexibility in circular DNA. 38 One interesting property of the model is that it is easily adaptable to describe further interactions such as the influence of solvent.…”