A single AT–GC exchange can modulate charge transfer-induced p53–DNA dissociation

Teo, Ruijie D.; Smithwick, Elizabeth R.; Migliore, Agostino; Beratan, David N.

doi:10.1039/c8cc09048c

Cited by 11 publications

(5 citation statements)

References 33 publications

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“…The electron-localization factors false{ μ normalm , μ normaln false} normalm ∈ normalD , normaln ∈ normalA for the analysis in Table were obtained by DFT calculations like those in ref but after optimizing the geometries of flavin and CPD in a continuum environment described by an enhanced COSMO solvation model , conceived to facilitate the geometry optimization and dynamics of molecular systems . In both the geometry optimization and the DFT single-point calculation, we used a relative dielectric constant of 25, which lies in the middle of the optimal range of 20–30 determined in ref . The geometry optimization and the following DFT calculation of the false{ μ normalm , μ normaln false} normalm ∈ normalD , normaln ∈ normalA set were carried out using the NWChem software. , Further details on the computational setup, as well as the coordinates of the optimized flavin and CPD moieties and the false{ μ normalm , μ normaln false} normalm ∈ normalD , normaln ∈ normalA values, are reported in Supporting Information Tables S3–S5.…”

Section: Methodsmentioning

confidence: 99%

Adenine Fine-Tunes DNA Photolyase’s Repair Mechanism

et al. 2023

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The comparative study of DNA repair by mesophilic and extremophilic photolyases helps us understand the evolution of these enzymes and their role in preserving life on our changing planet. The mechanism of repair of cyclobutane pyrimidine dimer lesions in DNA by electron transfer from the flavin adenine dinucleotide cofactor is the subject of intense interest. The role of adenine in mediating this process remains unresolved. Using microsecond molecular dynamics simulations, we find that adenine mediates the electron transfer in both mesophile and extremophile DNA photolyases through a similar mechanism. In fact, in all photolyases studied, the molecular conformations with the largest electronic couplings between the enzyme cofactor and DNA show the presence of adenine in 10−20% of the strongest-coupling tunneling pathways between the atoms of the electron donor and acceptor. Our theoretical analysis finds that adenine serves the critical role of fine-tuning rather than maximizing the donor−acceptor coupling within the range appropriate for the repair function.

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Section: Methodsmentioning

confidence: 99%

Adenine Fine-Tunes DNA Photolyase’s Repair Mechanism

et al. 2023

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“…The redistribution of initially produced base radical cations along DNA strands was explained by preferential trapping of the positive hole at guanine sites that act as efficient sinks. The charge transport (CT) chemistry that operates through both localized and delocalized hopping mechanisms (117)(118)(119)(120)(121) has been shown to be modulated by the presence of modified bases (122)(123)(124) or bound proteins (125)(126)(127). In the latter case, tyrosine and tryptophan when participating as amino acids in binding contacts were found to be oxidized by charge migration from DNA (125,128).…”

Section: One-electron Oxidation Dna-protein Cross-linking Chemistrymentioning

confidence: 99%

Capturing Protein–Nucleic Acid Interactions by High‐Intensity Laser‐Induced Covalent Cross‐Linking^†

Angelov

Boopathi

Lone

et al. 2022

Photochem & Photobiology

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Interactions of DNA with structural proteins such as histones, regulatory proteins and enzymes play a crucial role in major cellular processes such as transcription, replication and repair. The in vivo mapping and characterization of the binding sites of the involved biomolecules are of primary importance for a better understanding of genomic deployment that is implicated in tissue and developmental stagespecific gene expression regulation. The most powerful and commonly used approach to date is immunoprecipitation of chemically cross-linked chromatin (XChIP) coupled with sequencing analysis (ChIP-seq). While the resolution and the sensitivity of the high-throughput sequencing techniques have been constantly improved, little progress has been achieved in the cross-linking step. Because of its low efficiency, the use of the conventional UVC lamps remains very limited while the formaldehyde method was established as the "gold standard" cross-linking agent. Efficient biphotonic cross-linking of directly interacting nucleic acid-protein complexes by a single short UV laser pulse has been introduced as an innovative technique for overcoming limitations of conventionally used chemical and photochemical approaches. In this survey, the main available methods including the laser approach are critically reviewed for their ability to generate DNA-protein cross-links in vitro model systems and cells.

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“…The abundance and ubiquity of metalloproteins have attracted much scientific endeavors to understand the relationships between protein structures and functions [4,5], and translate that understanding into real-life applications [6,7]. While traditional molecular modeling approaches, such as classical molecular dynamics [8,9] and quantum mechanics/molecular mechanics (QM/MM) methods [10], have often been used to study these objectives, the usage of machine learning models has grown in popularity over the last decade [11], as metalloproteins can now be studied in a computationally inexpensive manner at a systems level. By designing and optimizing models to learn patterns and distinctions from training and validation data sets, these machine learning models can eventually predict the properties and behaviors of any new inputs (i.e., test sets).…”

Section: Introductionmentioning

confidence: 99%

Machine Learning Approaches for Metalloproteins

Wang

Teo

2022

Molecules

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Metalloproteins are a family of proteins characterized by metal ion binding, whereby the presence of these ions confers key catalytic and ligand-binding properties. Due to their ubiquity among biological systems, researchers have made immense efforts to predict the structural and functional roles of metalloproteins. Ultimately, having a comprehensive understanding of metalloproteins will lead to tangible applications, such as designing potent inhibitors in drug discovery. Recently, there has been an acceleration in the number of studies applying machine learning to predict metalloprotein properties, primarily driven by the advent of more sophisticated machine learning algorithms. This review covers how machine learning tools have consolidated and expanded our comprehension of various aspects of metalloproteins (structure, function, stability, ligand-binding interactions, and inhibitors). Future avenues of exploration are also discussed.

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A single AT–GC exchange can modulate charge transfer-induced p53–DNA dissociation

Cited by 11 publications

References 33 publications

Adenine Fine-Tunes DNA Photolyase’s Repair Mechanism

Adenine Fine-Tunes DNA Photolyase’s Repair Mechanism

Capturing Protein–Nucleic Acid Interactions by High‐Intensity Laser‐Induced Covalent Cross‐Linking^†

Machine Learning Approaches for Metalloproteins

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A single AT–GC exchange can modulate charge transfer-induced p53–DNA dissociation

Cited by 11 publications

References 33 publications

Adenine Fine-Tunes DNA Photolyase’s Repair Mechanism

Adenine Fine-Tunes DNA Photolyase’s Repair Mechanism

Capturing Protein–Nucleic Acid Interactions by High‐Intensity Laser‐Induced Covalent Cross‐Linking†

Machine Learning Approaches for Metalloproteins

Contact Info

Product

Resources

About

Capturing Protein–Nucleic Acid Interactions by High‐Intensity Laser‐Induced Covalent Cross‐Linking^†