NMR-based investigations into target DNA search processes of proteins

Iwahara, Junji; Zandarashvili, Levani; Kemme, Catherine A.; Esadze, Alexandre

doi:10.1016/j.ymeth.2018.05.004

Cited by 13 publications

(11 citation statements)

References 106 publications

(140 reference statements)

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“…More challenging, dynamic systems of biological macromolecules can be studied with current NMR techniques. Some NMR-based approaches have been developed for investigating the target DNA search by proteins [ 13 , 32 ]. Structural information on the proteins scanning DNA can be obtained through NMR experiments [ 64 – 69 ].…”

Section: Experimental Applicationsmentioning

confidence: 99%

“…Now, sliding of proteins on DNA is a well-established fact, which has been directly observed for many DNA-binding proteins in vitro and even in vivo by single-molecule methods [ 8 , 10 , 14 , 19 – 21 , 31 ]. Other methods such as nuclear magnetic resonance (NMR) spectroscopy [ 13 , 32 ], stopped-flow fluorescence [ 33 – 35 ], and elaborate biochemical approaches [ 36 – 42 ] also provide rich and quantitative information about how proteins locate their targets on DNA.…”

Section: Introductionmentioning

confidence: 99%

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Discrete-state stochastic kinetic models for target DNA search by proteins: Theory and experimental applications

Iwahara

Kolomeisky

2021

Biophysical Chemistry

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To perform their functions, transcription factors and DNA-repair/modifying enzymes randomly search DNA in order to locate their specific targets on DNA. Discrete-state stochastic kinetic models have been developed to explain how the efficiency of the search process is influenced by the molecular properties of proteins and DNA as well as by other factors such as molecular crowding. These theoretical models not only offer explanations on the relation of microscopic processes to macroscopic behavior of proteins, but also facilitate the analysis and interpretation of experimental data. In this review article, we provide an overview on discrete-state stochastic kinetic models and explain how these models can be applied to experimental investigations using stopped-flow, single-molecule, nuclear magnetic resonance (NMR), and other biophysical and biochemical methods.

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Section: Experimental Applicationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Discrete-state stochastic kinetic models for target DNA search by proteins: Theory and experimental applications

Iwahara

Kolomeisky

2021

Biophysical Chemistry

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“…In-cell NMR extends beyond proteins, and has been applied successfully to DNA [ 93 , 421 ] and RNA molecules [ 422 , 423 ]. Telomeric repeats have also been studied using target detected in-cell NMR [ 424 ].…”

Section: In-cell Nmr Approachesmentioning

confidence: 99%

NMR as a “Gold Standard” Method in Drug Design and Discovery

et al. 2020

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Studying disease models at the molecular level is vital for drug development in order to improve treatment and prevent a wide range of human pathologies. Microbial infections are still a major challenge because pathogens rapidly and continually evolve developing drug resistance. Cancer cells also change genetically, and current therapeutic techniques may be (or may become) ineffective in many cases. The pathology of many neurological diseases remains an enigma, and the exact etiology and underlying mechanisms are still largely unknown. Viral infections spread and develop much more quickly than does the corresponding research needed to prevent and combat these infections; the present and most relevant outbreak of SARS-CoV-2, which originated in Wuhan, China, illustrates the critical and immediate need to improve drug design and development techniques. Modern day drug discovery is a time-consuming, expensive process. Each new drug takes in excess of 10 years to develop and costs on average more than a billion US dollars. This demonstrates the need of a complete redesign or novel strategies. Nuclear Magnetic Resonance (NMR) has played a critical role in drug discovery ever since its introduction several decades ago. In just three decades, NMR has become a “gold standard” platform technology in medical and pharmacology studies. In this review, we present the major applications of NMR spectroscopy in medical drug discovery and development. The basic concepts, theories, and applications of the most commonly used NMR techniques are presented. We also summarize the advantages and limitations of the primary NMR methods in drug development.

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“…Typically, the chemical shift is attributed to the change in electron density around the proton caused by hydrogen bond formation [ 91 , 94 ]. Potential disadvantages of NMR involve the requirement of a high-field NMR spectrometer with a combination of multi-channel probe and multiple magnetic fields in certain circumstances [ 95 ].…”

Section: Spectroscopic Techniques Used In the Investigation Of Molmentioning

confidence: 99%

Molecular Interactions in Solid Dispersions of Poorly Water-Soluble Drugs

Tran

2020

Pharmaceutics

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Physicochemical characterization is a crucial step for the successful development of solid dispersions, including the determination of drug crystallinity and molecular interactions. Typically, the detection of molecular interactions will assist in the explanation of different drug performances (e.g., dissolution, solubility, stability) in solid dispersions. Various prominent reviews on solid dispersions have been reported recently. However, there is still no overview of recent techniques for evaluating the molecular interactions that occur within solid dispersions of poorly water-soluble drugs. In this review, we aim to overview common methods that have been used for solid dispersions to identify different bond formations and forces via the determination of interaction energy. In addition, a brief background on the important role of molecular interactions will also be described. The summary and discussion of methods used in the determination of molecular interactions will contribute to further developments in solid dispersions, especially for quick and potent drug delivery applications.

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NMR-based investigations into target DNA search processes of proteins

Cited by 13 publications

References 106 publications

Discrete-state stochastic kinetic models for target DNA search by proteins: Theory and experimental applications

Discrete-state stochastic kinetic models for target DNA search by proteins: Theory and experimental applications

NMR as a “Gold Standard” Method in Drug Design and Discovery

Molecular Interactions in Solid Dispersions of Poorly Water-Soluble Drugs

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