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Related Concept Videos

Cryo-electron Microscopy01:28

Cryo-electron Microscopy

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Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...
3.4K

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Fabrication of Micro-Patterned Chip with Controlled Thickness for High-Throughput Cryogenic Electron Microscopy
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Cryo-EM for Small Molecules Discovery, Design, Understanding, and Application.

Giovanna Scapin1, Clinton S Potter2, Bridget Carragher2

  • 1Department of Biochemical Engineering & Structure, Merck & Co., Inc., 2000 Galloping Hill Rd., Kenilworth, NJ 07033, USA.

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|August 14, 2018
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Summary

Cryoelectron microscopy (cryo-EM) offers a powerful approach for structure-based drug design (SBDD). Overcoming current challenges will unlock its full potential in accelerating drug discovery.

Keywords:
automationcryo-EMstructure-based drug discovery

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Area of Science:

  • Biochemistry
  • Structural Biology
  • Pharmacology

Background:

  • Structure-based drug design (SBDD) is crucial for identifying novel therapeutics.
  • Cryoelectron microscopy (cryo-EM) has emerged as a transformative technology in structural biology.

Purpose of the Study:

  • To provide a perspective on applying cryo-EM to SBDD.
  • To outline the requirements and current status of cryo-EM for SBDD.
  • To identify challenges hindering the full potential of cryo-EM in drug discovery.

Main Methods:

  • Review and synthesis of current literature on cryo-EM and SBDD.
  • Analysis of the essential components and prerequisites for successful SBDD using cryo-EM.

Main Results:

  • Cryo-EM is increasingly applicable to SBDD, providing high-resolution structural data.
  • Specific needs for SBDD, such as sample quality and data processing, are being addressed.
  • Significant challenges remain in areas like automation, data analysis, and accessibility.

Conclusions:

  • Cryo-EM holds immense promise for accelerating structure-based drug discovery.
  • Continued technological advancements and addressing current limitations are key to realizing this potential.
  • Collaboration and further development are essential for integrating cryo-EM seamlessly into the drug design pipeline.