Engineering the Entropy-driven Free-energy Landscape of a Dynamic Nanoporous Protein Assembly

Overview

Journal Nat Chem

Specialty Chemistry

Date 2018 May 2

PMID 29713036

Citations 18

Authors

Robert Alberstein

Yuta Suzuki

Francesco Paesani

F Akif Tezcan

Affiliations

Soon will be listed here.

Abstract

De novo design and construction of stimuli-responsive protein assemblies that predictably switch between discrete conformational states remains an essential but highly challenging goal in biomolecular design. We previously reported synthetic, two-dimensional protein lattices self-assembled via disulfide bonding interactions, which endows them with a unique capacity to undergo coherent conformational changes without losing crystalline order. Here, we carried out all-atom molecular dynamics simulations to map the free-energy landscape of these lattices, validated this landscape through extensive structural characterization by electron microscopy and established that it is predominantly governed by solvent reorganization entropy. Subsequent redesign of the protein surface with conditionally repulsive electrostatic interactions enabled us to predictably perturb the free-energy landscape and obtain a new protein lattice whose conformational dynamics can be chemically and mechanically toggled between three different states with varying porosities and molecular densities.

Citing Articles

Designed 2D protein crystals as dynamic molecular gatekeepers for a solid-state device.

Vijayakumar S, Alberstein R, Zhang Z, Lu Y, Chan A, Wahl C Nat Commun. 2024; 15(1):6326.

PMID: 39068153 PMC: 11283500. DOI: 10.1038/s41467-024-50567-8.

Heme-substituted protein assembly bridged by synthetic porphyrin: achieving controlled configuration while maintaining rotational freedom.

Inaba H, Shisaka Y, Ariyasu S, Sakakibara E, Ueda G, Aiba Y RSC Adv. 2024; 14(13):8829-8836.

PMID: 38495978 PMC: 10941265. DOI: 10.1039/d4ra01042f.

Lipidation Alters the Structure and Hydration of Myristoylated Intrinsically Disordered Proteins.

Ji J, Hossain M, Krueger E, Zhang Z, Nangia S, Carpentier B Biomacromolecules. 2023; 24(3):1244-1257.

PMID: 36757021 PMC: 10017028. DOI: 10.1021/acs.biomac.2c01309.

Protein Assembly by Design.

Zhu J, Avakyan N, Kakkis A, Hoffnagle A, Han K, Li Y Chem Rev. 2021; 121(22):13701-13796.

PMID: 34405992 PMC: 9148388. DOI: 10.1021/acs.chemrev.1c00308.

Ion-dependent protein-surface interactions from intrinsic solvent response.

Prelesnik J, Alberstein R, Zhang S, Pyles H, Baker D, Pfaendtner J Proc Natl Acad Sci U S A. 2021; 118(26).

PMID: 34172582 PMC: 8255788. DOI: 10.1073/pnas.2025121118.

References

Ebbinghaus S, Kim S, Heyden M, Yu X, Heugen U, Gruebele M . An extended dynamical hydration shell around proteins. Proc Natl Acad Sci U S A. 2007; 104(52):20749-52. PMC: 2410073. DOI: 10.1073/pnas.0709207104. View

Nguyen C, Young T, Gilson M . Grid inhomogeneous solvation theory: hydration structure and thermodynamics of the miniature receptor cucurbit[7]uril. J Chem Phys. 2012; 137(4):044101. PMC: 3416872. DOI: 10.1063/1.4733951. View

Tahara K, Nakatani K, Iritani K, De Feyter S, Tobe Y . Periodic Functionalization of Surface-Confined Pores in a Two-Dimensional Porous Network Using a Tailored Molecular Building Block. ACS Nano. 2016; 10(2):2113-20. DOI: 10.1021/acsnano.5b06483. View

Marsh J, Teichmann S . Structure, dynamics, assembly, and evolution of protein complexes. Annu Rev Biochem. 2014; 84:551-75. DOI: 10.1146/annurev-biochem-060614-034142. View

Zhu F, Hummer G . Convergence and error estimation in free energy calculations using the weighted histogram analysis method. J Comput Chem. 2011; 33(4):453-65. PMC: 3271861. DOI: 10.1002/jcc.21989. View

Butler S, Hollen S, Cao L, Cui Y, Gupta J, Gutierrez H . Progress, challenges, and opportunities in two-dimensional materials beyond graphene. ACS Nano. 2013; 7(4):2898-926. DOI: 10.1021/nn400280c. View

Suzuki Y, Cardone G, Restrepo D, Zavattieri P, Baker T, Tezcan F . Self-assembly of coherently dynamic, auxetic, two-dimensional protein crystals. Nature. 2016; 533(7603):369-73. PMC: 4991361. DOI: 10.1038/nature17633. View

Yeates T . Geometric Principles for Designing Highly Symmetric Self-Assembling Protein Nanomaterials. Annu Rev Biophys. 2017; 46:23-42. DOI: 10.1146/annurev-biophys-070816-033928. View

Sontz P, Bailey J, Ahn S, Tezcan F . A Metal Organic Framework with Spherical Protein Nodes: Rational Chemical Design of 3D Protein Crystals. J Am Chem Soc. 2015; 137(36):11598-601. DOI: 10.1021/jacs.5b07463. View

10.

Heyden M, Sun J, Funkner S, Mathias G, Forbert H, Havenith M . Dissecting the THz spectrum of liquid water from first principles via correlations in time and space. Proc Natl Acad Sci U S A. 2010; 107(27):12068-73. PMC: 2901429. DOI: 10.1073/pnas.0914885107. View

11.

Norn C, Andre I . Computational design of protein self-assembly. Curr Opin Struct Biol. 2016; 39:39-45. DOI: 10.1016/j.sbi.2016.04.002. View

12.

Koga N, Tatsumi-Koga R, Liu G, Xiao R, Acton T, Montelione G . Principles for designing ideal protein structures. Nature. 2012; 491(7423):222-7. PMC: 3705962. DOI: 10.1038/nature11600. View

13.

Song W, Tezcan F . A designed supramolecular protein assembly with in vivo enzymatic activity. Science. 2014; 346(6216):1525-8. DOI: 10.1126/science.1259680. View

14.

Huggins D . Comparing distance metrics for rotation using the k-nearest neighbors algorithm for entropy estimation. J Comput Chem. 2013; 35(5):377-85. PMC: 4238811. DOI: 10.1002/jcc.23504. View

15.

Giovambattista N, Rossky P, Debenedetti P . Effect of temperature on the structure and phase behavior of water confined by hydrophobic, hydrophilic, and heterogeneous surfaces. J Phys Chem B. 2009; 113(42):13723-34. DOI: 10.1021/jp9018266. View

16.

Huber C, Liu J, Egelseer E, Moll D, Knoll W, Sleytr U . Heterotetramers formed by an S-layer-streptavidin fusion protein and core-streptavidin as a nanoarrayed template for biochip development. Small. 2006; 2(1):142-50. DOI: 10.1002/smll.200500147. View

17.

Joshi R, Carbone P, Wang F, Kravets V, Su Y, Grigorieva I . Precise and ultrafast molecular sieving through graphene oxide membranes. Science. 2014; 343(6172):752-4. DOI: 10.1126/science.1245711. View

18.

Ringler P, Schulz G . Self-assembly of proteins into designed networks. Science. 2003; 302(5642):106-9. DOI: 10.1126/science.1088074. View

19.

Sinclair J, Davies K, Venien-Bryan C, Noble M . Generation of protein lattices by fusing proteins with matching rotational symmetry. Nat Nanotechnol. 2011; 6(9):558-62. DOI: 10.1038/nnano.2011.122. View

20.

Hedstrom L . Serine protease mechanism and specificity. Chem Rev. 2002; 102(12):4501-24. DOI: 10.1021/cr000033x. View