MicroED for the study of protein-ligand interactions and the potential for drug discovery

Lisa J Clark; Guanhong Bu; Brent L Nannenga; Tamir Gonen

doi:10.1038/s41570-021-00332-y

MicroED for the study of protein-ligand interactions and the potential for drug discovery

Nat Rev Chem. 2021 Dec;5(12):853-858. doi: 10.1038/s41570-021-00332-y. Epub 2021 Oct 27.

Authors

Lisa J Clark¹, Guanhong Bu^{2

3}, Brent L Nannenga^{4

5}, Tamir Gonen^{6

7

8}

Affiliations

¹ Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, USA.
² Chemical Engineering, School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ, USA.
³ Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ, USA.
⁴ Chemical Engineering, School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ, USA. brent.nannenga@asu.edu.
⁵ Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ, USA. brent.nannenga@asu.edu.
⁶ Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, USA. tgonen@g.ucla.edu.
⁷ Department of Physiology, University of California, Los Angeles, Los Angeles, CA, USA. tgonen@g.ucla.edu.
⁸ Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA, USA. tgonen@g.ucla.edu.

PMID: 37117388
DOI: 10.1038/s41570-021-00332-y

Abstract

Microcrystal electron diffraction (MicroED) is an electron cryo-microscopy (cryo-EM) technique used to determine molecular structures with crystals that are a millionth the size needed for traditional single-crystal X-ray crystallography. An exciting use of MicroED is in drug discovery and development, where it can be applied to the study of proteins and small molecule interactions, and for structure determination of natural products. The structures are then used for rational drug design and optimization. In this Perspective, we discuss the current applications of MicroED for structure determination of protein-ligand complexes and potential future applications in drug discovery.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Crystallography, X-Ray
Drug Discovery
Electrons*
Ligands
Proteins* / chemistry

Substances

Ligands
Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding