title: Resolution advances in cryo-EM enable application to drug discovery.
abstract: The prospect that the structures of protein assemblies, small and large, can be determined using cryo-electron microscopy (cryo-EM) is beginning to transform the landscape of structural biology and cell biology. Great progress is being made in determining 3D structures of biological assemblies ranging from icosahedral viruses and helical arrays to small membrane proteins and protein complexes. Here, we review recent advances in this field, focusing especially on the emerging use of cryo-EM in mapping the binding of drugs and inhibitors to protein targets, an application that requires structure determination at the highest possible resolutions. We discuss methods used to evaluate the information contained in cryo-EM density maps and consider strengths and weaknesses of approaches currently used to measure map resolution.
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: ss1@nih.gov.
authors.forename: Sriram
authors.initials: S
authors.lastname: Subramaniam
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Earl
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Veronica
authors.initials: V
authors.lastname: Falconieri
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jacqueline Ls
authors.initials: JL
authors.lastname: Milne
authors.affiliation: University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Egelman
mesh_terms: D000818:Animals; D020285:Cryoelectron Microscopy / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008024:Ligands; D059629:Signal-To-Noise Ratio; D054852:Small Molecule Libraries / Q000378:metabolism
chemical_list: D008024:Ligands; D054852:Small Molecule Libraries