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Updated: Jan 6, 2026

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps
Published on: July 19, 2024
Modeling membrane proteins based on low-resolution electron microscopy maps: a template for the TM domains of the
Thijs Beuming1, Harel Weinstein
1Department of Physiology and Biophysics, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
Abstract:
The availability of both EM and high-resolution crystallographic data for several membrane proteins (MPs) permits a detailed evaluation of the ability of molecular modeling techniques to complement EM data in the development of models of MPs. A protocol for this purpose is presented, consisting of (1) identifying transmembrane (TM) domains from sequence; (2) assigning buried and lipid-exposed faces of the TM domains; and (3) assembling the TM domains into a bundle, based on geometric restraints obtained from the EM data. The protocol is validated by predicting the structures of several 7- and 12-TM MPs to within 3-5 A r.m.s.d. from their crystal structures. The protocol is applied to generate a model of the oxalate transporter OxlT, for which a high-resolution structure is not yet available.
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