Current Experimental Methods for Characterizing Protein–Protein Interactions

Zhou, Mi; Li, Qing; Wang, Renxiao

doi:10.1002/cmdc.201500495

Cited by 113 publications

(102 citation statements)

References 268 publications

(253 reference statements)

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“…These interactions are typically characterized via the binding free energy . The binding free energy is a complex quantity composed of various energy terms and many methods have been developed to predict it, including approaches for modeling the binding free energy changes caused by mutations . Among the various energy terms contributing to the binding free energy, the electrostatics plays prominent role due to its long‐range nature .…”

Section: Introductionmentioning

confidence: 99%

Electrostatic component of binding energy: Interpreting predictions from poisson–boltzmann equation and modeling protocols

Chakavorty

Alexov

2016

J Comput Chem

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Macromolecular interactions are essential for understanding numerous biological processes and are typically characterized by the binding free energy. Important component of the binding free energy is the electrostatics, which is frequently modeled via the solutions of the Poisson-Boltzmann Equations (PBE). However, numerous works have shown that the electrostatic component (ΔΔGelec) of binding free energy is very sensitive to the parameters used and modeling protocol. This prompted some researchers to question the robustness of PBE in predicting ΔΔGelec. We argue that the sensitivity of the absolute ΔΔGelec calculated with PBE using different input parameters and definitions does not indicate PBE deficiency, rather this is what should be expected. We show how the apparent sensitivity should be interpreted in terms of the underlying changes in several numerous and physical parameters. We demonstrate that PBE approach is robust within each considered force field (CHARMM-27, AMBER-94 and OPLS-AA) once the corresponding structures are energy minimized. This observation holds despite of using two different molecular surface definitions, pointing again that PBE delivers consistent results within particular force field. The fact that PBE delivered ΔΔGelec values may differ if calculated with different modeling protocols is not a deficiency of PBE, but natural results of the differences of the force field parameters and potential functions for energy minimization. In addition, while the absolute ΔΔGelec values calculated with different force field differ, their ordering remains practically the same allowing for consistent ranking despite of the force field used.

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Section: Introductionmentioning

confidence: 99%

Electrostatic component of binding energy: Interpreting predictions from poisson–boltzmann equation and modeling protocols

Chakavorty

Alexov

2016

J Comput Chem

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“…Currently, only a few methods enable direct and label-free screening, 35,36 including drug affinity responsive target stability (DARTS), 37,38 and surface plasmon resonance (SPR) technology. 39 In this report, we demonstrated that, as proof-of-concept, epitope editing could be used to seek ligands for a target of interest, which requires no modification/tagging and no extra equipment. In our exploratory investigation, several examples were successfully demonstrated, including Aβ peptides, tau and PD-L1…”

Section: Discussionmentioning

confidence: 89%

A screening platform based on epitope editing for drug discovery

Zhu

Yang

Van

et al. 2019

Preprint

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The interaction between an antibody and its epitope has been daily utilized in various biological studies; however it has been rarely explored whether small molecules can alter the interaction. We discovered that small molecules could alter/edit surface properties of amyloid beta (Aβ) epitopes, and consequently inhibit or enhance corresponding antibody recognition. Remarkably, this editing effect could generate functional changes including protein aggregation behaviors, cell cytokine secreting and in vivo microglia activation. According to this discovery, we proposed a screen 2 platform based on epitope editing for drug discovery (SPEED). With a small library of compounds, we validated that SPEED could be used to seek new leads for Aβ species.We also demonstrated that this platform could potentially be extended to other targets including tau protein and PD-L1 protein. The SPEED is a simple, fast and label-free screening method. We believe that the SPEED strategy could be universally applicable for seeking and validating drug candidates and imaging ligands.

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“…110, and how do key proteins in living cells interact with one another under physiological and pathological conditions in vivo ? 111. In summary, the potential capabilities of the BphP1-based single-wavelength differential method are only beginning to be recognized and will be fully explored in the future.…”

Section: Concluding Remarks and Outlookmentioning

confidence: 99%

Advances in Imaging Techniques and Genetically Encoded Probes for Photoacoustic Imaging

Liu¹,

Gong²,

Lin³

et al. 2016

Theranostics

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Photoacoustic (PA) imaging is a rapidly emerging biomedical imaging modality that is capable of visualizing cellular and molecular functions with high detection sensitivity and spatial resolution in deep tissue. Great efforts and progress have been made on the development of various PA imaging technologies with improved resolution and sensitivity over the past two decades. Various PA probes with high contrast have also been extensively developed, with many important biomedical applications. In comparison with chemical dyes and nanoparticles, genetically encoded probes offer easier labeling of defined cells within tissues or proteins of interest within a cell, have higher stability in vivo, and eliminate the need for delivery of exogenous substances. Genetically encoded probes have thus attracted increasing attention from researchers in engineering and biomedicine. In this review, we aim to provide an overview of the existing PA imaging technologies and genetically encoded PA probes, and describe further improvements in PA imaging techniques and the near-infrared photochromic protein BphP1, the most sensitive genetically encoded probe thus far, as well as the potential biomedical applications of BphP1-based PA imaging in vivo.

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Current Experimental Methods for Characterizing Protein–Protein Interactions

Cited by 113 publications

References 268 publications

Electrostatic component of binding energy: Interpreting predictions from poisson–boltzmann equation and modeling protocols

Electrostatic component of binding energy: Interpreting predictions from poisson–boltzmann equation and modeling protocols

A screening platform based on epitope editing for drug discovery

Advances in Imaging Techniques and Genetically Encoded Probes for Photoacoustic Imaging

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