Biology subjects

Demir, B.

Publications and source records attributed to Demir, B..

3 recordsLinked to original sources

bioRxiv2024

Targeting miRNA for Colorectal Cancer: In Silico Identification and Physics-based De Novo Modeling of Oncogenic miR-135b for Small Molecule RNA Therapy

Colorectal cancer is one of the leading causes of cancer deaths worldwide. In the current study, we have identified miR-135b, a microRNA to be differentially expressed in colorectal cancer, through an analysis of the differentially expressed miRNAs from the Gene Expression Omnibus database. Subsequently, the target genes associated with miR-135b were pinpointed, and pathway and functional enrichment analyses were performed to gain a comprehensive understanding of the underlying biological processes involved. A de novo three-dimensional model of its tertiary structure was developed for small-molecule targeting at the Dicer cleavage site. Dicer binds to the terminal loop region of the pre-miRNA and cleaves to generate double stranded miRNA duplex. The miRNA duplex is unwound, one of the strands, guide miRNA, is loaded into the RNA-induced silencing complex (RISC) for miRNA-mRNA target interaction and post-transcriptional gene silencing. Following results from molecular docking simulations initiated with the ChemDiv miRNA-targeted small molecule library ([~]20.000 compounds), top-scoring compounds commercial analogues were then searched within the ZINC library using SwissSimilarity. These analogues were docked to the Dicer cleavage site and their optimized docking scores were obtained. These top-scoring molecules were then subject to all-atom molecular dynamics simulations and post-simulation analyses were conducted to assess the dynamic interactions between the miRNA and the selected hit ligands.

bioinformatics↗

bioRxiv2023

A Computational Study of the Role of Counterions and Solvent Dielectric in Determining the Conductance of B-DNA

DNA naturally exists in a solvent environment, comprised of water and salt molecules such as sodium, potassium, magnesium, etc. Along with the sequence, the solvent conditions become a vital factor determining DNA structure and thus its conductance. Over the last two decades, researchers have measured DNA conductivity both in hydrated and almost dry (dehydrated) conditions. However, due to experimental limitations (the precise control of the environment), it is very difficult to analyze the conductance results in terms of individual contributions of the environment. Therefore, modeling studies can help us to gain a valuable understanding of various factors playing a role in charge transport phenomena. DNA naturally has negative charges located at the phosphate groups in the backbone, which provides both the connections between the base pairs and the structural support for the double helix. Positively charged ions such as the Sodiumion (Na+), one of the most commonly used counterions, balance the negative charges at the backbone. This modeling study investigates the role of counterions both with and without the solvent (water) environment on charge transport through double-stranded DNA. Our computational experiments show that in dry DNA, the presence of counterions affects electron transmission at the lowest unoccupied molecular orbital energies. However, in solution, the counterions have a negligible role in transmission. Using the polarizable continuum model calculations, we demonstrate that the transmission is significantly higher at both the highest occupied and lowest unoccupied molecular orbital energies in a water environment as opposed to in a dry one. Moreover, calculations also show that the energy levels of neighboring bases are more closely aligned to ease electron flow in the solution.

biophysics↗

bioRxiv2023

DNA nanopores as artificial membrane channels for origami based bioelectronics

Biological membrane channels mediate information exchange between cells and facilitate molecular recognition1-4. While tuning the shape and function of membrane channels for precision molecular sensing via de-novo routes is complex, an even more significant challenge is interfacing membrane channels with electronic devices for signal readout5-8. This challenge at the biotic-abiotic interface results in low efficiency of information transfer - one of the major barriers to the continued development of high-performance bioelectronic devices9. To this end, we integrate membrane spanning DNA nanopores with bioprotonic contacts to create programmable, modular, and efficient artificial ion-channel interfaces that resolve the iono-electronic disparity between the biotic environment and electronics. Through simulations and experiments, we show that cholesterol modified DNA nanopores spontaneously and with remarkable affinity span the lipid bilayer formed over the planar bio-protonic electrode surface and mediate proton transport across the bilayer. Using the ability to easily modify DNA nanostructures, we illustrate that this bioelectronic device can be programmed for electronic recognition of biomolecular signals such as presence of Streptavidin, without disrupting the native environment of the biomolecule. We anticipate this robust biotic-abiotic interface will allow facile electronic measurement of inter-cellular ionic communication and also open the door for active control of cell behavior through externally controlled selective gating of the channels.

bioengineering↗