Helical Protein Assemblies by Design

Project Personnel

Vincent Conticello

Principal Investigator

Emory University

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Edward Egelman

University of Virginia

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Gevorg Grigoryan

Dartmouth College

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Funding Divisions

Division of Materials Research (DMR), Division of Chemistry (CHE), Office of Multidisciplinary Activities (OMA)

The ability to emulate such functions by designing synthetic protein assemblies would transform modern molecular science, with far-reaching applications including locomotion, controlled release, directional transport, dynamic switching, and shape-selective catalysis. In this project, a novel intellectual framework for the targeted design of synthetic protein assemblies at atomic-level accuracy will be established, validated, and made available to the research community. Enabled by the combined expertise of the three investigators involved, this approach will merge significant advances in modeling and computational design with never-before-possible experimental techniques for structural determination of protein assemblies at the atomic level. On the way to developing this framework, fundamental questions of acute significance to biology, chemistry, and materials science will be addressed: from development of an understanding of the functional roles of native biological assemblies to construction of synthetic assemblies for technological applications. Students (graduate and undergraduate), postdoctorals, and faculty involved in this project will gain experience in a variety of computational, synthetic, and analytical methods in research areas of fundamental technological interest that will prepare them well for future scientific careers. An exchange program between the three academic institutions (Emory University, University of Virginia, and Dartmouth College) will be established that will permit students and postdoctorals to become involved in the different aspects of this research project.

Publications

Phenol-soluble modulins PSMα3 and PSMβ2 form nanotubes that are cross-α amyloids
M. A. B. Kreutzberger, S. Wang, L. C. Beltran, A. Tuachi, X. Zuo, E. H. Egelman, and V. P. Conticello
5/9/2022
Cryo-EM of Helical Polymers
F. Wang, O. Gnewou, A. Solemanifar, V. P. Conticello, and E. H. Egelman
2/8/2022
Structures of synthetic helical filaments and tubes based on peptide and peptido-mimetic polymers
J. G. Miller, S. A. Hughes, C. Modlin, and V. P. Conticello
1/1/2022
Deterministic chaos in the self-assembly of β sheet nanotubes from an amphipathic oligopeptide
F. Wang, O. Gnewou, S. Wang, T. Osinski, X. Zuo, E. H. Egelman, and V. P. Conticello
10/1/2021
Structural analysis of cross α-helical nanotubes provides insight into the designability of filamentous peptide nanomaterials
F. Wang, O. Gnewou, C. Modlin, L. C. Beltran, C. Xu, Z. Su, P. Juneja, G. Grigoryan, E. H. Egelman, and V. P. Conticello
1/18/2021
Assessing the effect of aromatic residue placement on the α-helical peptide structure and nanofibril formation of 21-mer peptides
A. Solemanifar, T. A. H. Nguyen, B. Laycock, H. M. Shewan, B. C. Donose, and R. C. G. Creasey
1/1/2020
Ambidextrous helical nanotubes from self-assembly of designed helical hairpin motifs
S. A. Hughes, F. Wang, S. Wang, M. A. B. Kreutzberger, T. Osinski, A. Orlova, J. S. Wall, X. Zuo, E. H. Egelman, and V. P. Conticello
7/1/2019
Protein structural motifs in prediction and design
C. O. Mackenzie, and G. Grigoryan
6/1/2017
Tertiary alphabet for the observable protein structural universe
C. O. Mackenzie, J. Zhou, and G. Grigoryan
11/3/2016

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Designing Materials to Revolutionize and Engineer our Future (DMREF)