Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

An automatic method for predicting transmembrane protein structures using cryo-EM and evolutionary data.

Sarel J Fleishman1, Susan Harrington, Richard A Friesner

  • 1Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat-Aviv 69978, Israel.

Biophysical Journal
|September 2, 2004
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

DIO3 associates with sorting nexins and endosomal trafficking networks in ovarian cancer.

Cellular oncology (Dordrecht, Netherlands)·2026
Same author

A functional investigation of antibody Fc-FcRn variant binding guided by <i>in silico</i> free energy perturbation methods.

bioRxiv : the preprint server for biology·2026
Same author

Proteome-wide prediction of interactions between structured domains and peptide motifs reveals functionally coherent subnetworks.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

PrePPI - Structure-based Prediction of Protein-protein Interactomes and Networks.

Journal of molecular biology·2026
Same author

Trafficking of the human Na<sup>+</sup>/H<sup>+</sup> antiporter NHA2 to the plasma membrane requires cornichon COPII cargo receptors.

Protein science : a publication of the Protein Society·2026
Same author

Interpretable prediction of zinc ion location in proteins with ZincSight.

Protein science : a publication of the Protein Society·2025
Same journal

Enhanced-Sampling Simulations Reveal Distinct Intermediates in SARS-CoV-2 FSE Pseudoknot Interconversion.

Biophysical journal·2026
Same journal

Structure-based simulations of the full Flock House virus capsid reveal pathways and energetics of an infection-critical peptide externalization event.

Biophysical journal·2026
Same journal

Quantifying the Peripheral Surface Information Entropy from Conformational Ensembles of Globular Protein-Peptide Complexes.

Biophysical journal·2026
Same journal

Anisotropic unbinding and location-dependent hovering of a kinesin motor head over microtubule.

Biophysical journal·2026
Same journal

Kinesin-5/Cut7 C-terminal tail phosphorylation influence on motor regulation through multi-scale molecular modeling.

Biophysical journal·2026
Same journal

Dynamic conformations of fluorophores on self-labeling protein tags.

Biophysical journal·2026
See all related articles

Determining transmembrane protein structures is challenging. This study introduces a computational method using cryo-electron microscopy data to orient transmembrane helices, enabling approximate model structure determination.

Area of Science:

  • Structural biology
  • Computational biophysics
  • Membrane protein research

Background:

  • Transmembrane (TM) domains of integral membrane proteins often form alpha-helix bundles.
  • Experimental structure determination of TM domains at high resolution is difficult.
  • Cryo-electron microscopy (cryo-EM) provides intermediate to low-resolution structures, revealing packing but not individual amino acid positions.

Purpose of the Study:

  • To develop computational methods for orienting TM helices within membrane proteins.
  • To leverage evolutionary information about lipid-exposed faces versus core regions for helix orientation.
  • To enable approximate TM domain structure determination when high-resolution experimental data is unavailable.

Main Methods:

  • Development of score functions and automated methods for TM helix orientation based on evolutionary variability and charge distribution.

Related Experiment Videos

  • Parameterization using the native structure of bacteriorhodopsin.
  • Testing the method on diverse proteins like the acetylcholine receptor and rhodopsin, using cryo-EM derived helix locations and tilt angles.

    • Main Results:

    • The computational method successfully oriented TM helices, achieving predicted structures within 1.5-3.5 Å of native states for tested proteins.
    • The method demonstrated effectiveness even for proteins with different sequences and architectures compared to the training set.
    • Scoring functions could distinguish near- from far-from-native conformations in proteins with short loops, without relying on cryo-EM constraints.

    Conclusions:

    • The computational approach, combined with cryo-EM data, can yield approximate TM domain structures for proteins with sufficient homologous sequences.
    • This method offers a valuable tool for structural biologists studying membrane proteins where high-resolution experimental data is limited.
    • The scoring functions show promise for conformational selection even without precise helix positional data.