Discovery of fragments inducing conformational effects in dynamic proteins using a second-harmonic generation biosensor

Fitzgerald, Edward A.; Butko, Margaret T.; Boronat, Pierre; Cederfelt, Daniela; Abramsson, Mia; Ludviksdottir, Hildur; Muijlwijk‐Koezen, Jacqueline E. van; Esch, Iwan J. P. de; Dobritzsch, Doreen; Young, Tracy A.; Danielson, U. Helena

doi:10.1039/d0ra09844b

Cited by 7 publications

(6 citation statements)

References 35 publications

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“…Second-harmonic generation (SHG) is another biophysical screening method that has recently been used in combination with fragment libraries. [27,73,74] The method requires labeling the target molecule with a dye, immobilizing it, and then radiating it with 800 nm red light (Figure 15). The second-harmonic generation causes two incoming photons to be absorbed by the dye and then emit 400 nm light, and the intensity of the emitted light is dependent on the position of the dye relative to the surface normal.…”

Section: Second-harmonic Generationmentioning

confidence: 99%

“…Second‐harmonic generation (SHG) is another biophysical screening method that has recently been used in combination with fragment libraries [27,73,74] . The method requires labeling the target molecule with a dye, immobilizing it, and then radiating it with 800 nm red light (Figure 15).…”

Section: Future Perspectivesmentioning

confidence: 99%

“…Discovery of fragments inducing conformational effects in dynamic proteins using a second-harmonic generation biosensor. [27] Birman et al: Second-harmonic generation-based methods to detect and characterize ligand-induced RNA conformational changes. [28] Cryogenic electron microscopy (Cryo-EM) (future perspective)…”

Section: Fitzgerald Et Almentioning

confidence: 99%

“…FitzGerald et al . : Discovery of fragments inducing conformational effects in dynamic proteins using a second‐ harmonic generation biosensor [27] . Birman et al .…”

Section: Introductionmentioning

confidence: 99%

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Fragment‐Based Drug Discovery for RNA Targets

et al. 2021

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Rapid development within the fields of both fragment-based drug discovery (FBDD) and medicinal targeting of RNA provides possibilities for combining technologies and methods in novel ways. This review provides an overview of fragment-based screening (FBS) against RNA targets, including a discussion of the most recently used screening and hit validation methods such as NMR spectroscopy, X-ray crystallography, and virtual screening methods. A discussion of fragment library design based on research from small-molecule RNA binders provides an overview on both the currently limited guidelines within RNA-targeting fragment library design, and future possibilities. Finally, future perspectives are provided on screening and hit validation methods not yet used in combination with both fragment screening and RNA targets.

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Section: Second-harmonic Generationmentioning

confidence: 99%

Section: Future Perspectivesmentioning

confidence: 99%

Section: Fitzgerald Et Almentioning

confidence: 99%

“…FitzGerald et al . : Discovery of fragments inducing conformational effects in dynamic proteins using a second‐ harmonic generation biosensor [27] . Birman et al .…”

Section: Introductionmentioning

confidence: 99%

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Fragment‐Based Drug Discovery for RNA Targets

et al. 2021

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“…GCI is applicable to soluble [28] and membrane bound proteins, [29][30][31][32] RNA targets, [33] and complex multicomponent assemblies. [34] GCI also offers the critical advantage of high kinetic sensitivity compared to traditional SPR, [35,36] thus enabling the detection of weak binding events, which are typically associated with primary screening hits. This high sensitivity is maximized by the waveRAPID® (Repeated Analyte Pulses of Increasing Duration) technology, [37] which accelerates the acquisition of binding kinetic parameters by screening compounds at a single concentration and varying the injection time on the sensor chip.…”

Section: Introductionmentioning

confidence: 99%

Accelerating BRPF1b hit identification with BioPhysical and Active Learning Screening (BioPALS)

Pal,

Nare,

Rao

et al. 2024

ChemMedChem

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We report the development of BioPhysical and Active Learning Screening (BioPALS); a rapid and versatile hit identification protocol combining AI‐powered virtual screening with a GCI‐driven biophysical confirmation workflow. Its application to the BRPF1b bromodomain afforded a range of novel micromolar binders with favorable ADMET parameters. In addition to the excellent in silico/in vitro confirmation rate demonstrated with BRPF1b, binding kinetics are determined, and binding topologies predicted for all hits. BioPALS is a lean, data‐rich, and standardized approach to hit identification applicable to wide range of biological targets.

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Plasmonic Nanostars: Unique Properties That Distinguish Them from Spherical Nanoparticles from a Biosensing Perspective

Tukova,

Nguyen,

Garcia‐Bennett

et al. 2024

Advanced Optical Materials

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Over the past three decades, plasmonic nanostructures, particularly spherical ones, have seen remarkable advancements. Recently, attention has shifted toward anisotropic nanoparticles, especially star‐shaped/branched structures such as plasmonic nanostars (PNS), due to their distinct properties. PNS offers superior electromagnetic enhancement effects, larger surface areas, and as well as non‐linear and unusual photothermal properties, setting them apart from spherical counterparts. Despite significant progress in synthetic methods and characterization of the particles, challenges remain in transitioning PNS technology into practical use. In this perspective article, the distinctive attributes of PNS in biosensing applications are discussed, beginning with an exploration of synthesis methodologies. Their optoelectronic properties are examined and discussed how these properties influence their interaction with different molecules from a biosensing perspective. With a focus on PNS, detailed insights are offered into their unique properties, current applications, and future potential. By fostering discussion and understanding of PNS development, this article aims to facilitate the translation of PNS technology into practical applications, encouraging targeted improvements and advancements.

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Discovery of fragments inducing conformational effects in dynamic proteins using a second-harmonic generation biosensor

Abstract: Fragments inducing conformational changes identified at a dynamic region of AChBP.

Cited by 7 publications

References 35 publications

Fragment‐Based Drug Discovery for RNA Targets

Fragment‐Based Drug Discovery for RNA Targets

Accelerating BRPF1b hit identification with BioPhysical and Active Learning Screening (BioPALS)

Plasmonic Nanostars: Unique Properties That Distinguish Them from Spherical Nanoparticles from a Biosensing Perspective

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