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1. Structural predictions of protein–DNA binding: MELD-DNA

   https://doi.org/10.1093/nar/gkad013  

   Esmaeeli, Reza; Bauzá, Antonio; Perez, Alberto (February 2023, Nucleic Acids Research)

   Abstract Structural, regulatory and enzymatic proteins interact with DNA to maintain a healthy and functional genome. Yet, our structural understanding of how proteins interact with DNA is limited. We present MELD-DNA, a novel computational approach to predict the structures of protein–DNA complexes. The method combines molecular dynamics simulations with general knowledge or experimental information through Bayesian inference. The physical model is sensitive to sequence-dependent properties and conformational changes required for binding, while information accelerates sampling of bound conformations. MELD-DNA can: (i) sample multiple binding modes; (ii) identify the preferred binding mode from the ensembles; and (iii) provide qualitative binding preferences between DNA sequences. We first assess performance on a dataset of 15 protein–DNA complexes and compare it with state-of-the-art methodologies. Furthermore, for three selected complexes, we show sequence dependence effects of binding in MELD predictions. We expect that the results presented herein, together with the freely available software, will impact structural biology (by complementing DNA structural databases) and molecular recognition (by bringing new insights into aspects governing protein–DNA interactions). 

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2. Exploiting DNA Endonucleases to Advance Mechanisms of DNA Repair

   https://doi.org/10.3390/biology10060530  

   Thompson, Marlo K.; Sobol, Robert W.; Prakash, Aishwarya (June 2021, Biology)

   The earliest methods of genome editing, such as zinc-finger nucleases (ZFN) and transcription activator-like effector nucleases (TALENs), utilize customizable DNA-binding motifs to target the genome at specific loci. While these approaches provided sequence-specific gene-editing capacity, the laborious process of designing and synthesizing recombinant nucleases to recognize a specific target sequence, combined with limited target choices and poor editing efficiency, ultimately minimized the broad utility of these systems. The discovery of clustered regularly interspaced short palindromic repeat sequences (CRISPR) in Escherichia coli dates to 1987, yet it was another 20 years before CRISPR and the CRISPR-associated (Cas) proteins were identified as part of the microbial adaptive immune system, by targeting phage DNA, to fight bacteriophage reinfection. By 2013, CRISPR/Cas9 systems had been engineered to allow gene editing in mammalian cells. The ease of design, low cytotoxicity, and increased efficiency have made CRISPR/Cas9 and its related systems the designer nucleases of choice for many. In this review, we discuss the various CRISPR systems and their broad utility in genome manipulation. We will explore how CRISPR-controlled modifications have advanced our understanding of the mechanisms of genome stability, using the modulation of DNA repair genes as examples. 

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3. DNA Sequencing: Clinical Applications of New DNA Sequencing Technologies

   https://doi.org/10.1161/CIRCULATIONAHA.110.972828  

   Dewey, Frederick E.; Pan, Stephen; Wheeler, Matthew T.; Quake, Stephen R.; Ashley, Euan A. (February 2012, Circulation)
4. Mechanical Flexibility of DNA: A Quintessential Tool for DNA Nanotechnology

   https://doi.org/10.3390/s20247019  

   Saran, Runjhun; Wang, Yong; Li, Isaac T. (December 2020, Sensors)

   null (Ed.)

   The mechanical properties of DNA have enabled it to be a structural and sensory element in many nanotechnology applications. While specific base-pairing interactions and secondary structure formation have been the most widely utilized mechanism in designing DNA nanodevices and biosensors, the intrinsic mechanical rigidity and flexibility are often overlooked. In this article, we will discuss the biochemical and biophysical origin of double-stranded DNA rigidity and how environmental and intrinsic factors such as salt, temperature, sequence, and small molecules influence it. We will then take a critical look at three areas of applications of DNA bending rigidity. First, we will discuss how DNA’s bending rigidity has been utilized to create molecular springs that regulate the activities of biomolecules and cellular processes. Second, we will discuss how the nanomechanical response induced by DNA rigidity has been used to create conformational changes as sensors for molecular force, pH, metal ions, small molecules, and protein interactions. Lastly, we will discuss how DNA’s rigidity enabled its application in creating DNA-based nanostructures from DNA origami to nanomachines. 

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5. DNA Intercalation Facilitates Efficient DNA-Targeted Covalent Binding of Phenanthriplatin

   https://doi.org/10.1021/jacs.8b10252  

   Almaqwashi, Ali A.; Zhou, Wen; Naufer, M. Nabuan; Riddell, Imogen A.; Yilmaz, Ömer H.; Lippard, Stephen J.; Williams, Mark C. (December 2018, Journal of the American Chemical Society)