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Computational and Experimental Protocols to Study Cyclo-dihistidine Self- and Co-assembly: Minimalistic Bio-assemblies with Enhanced Fluorescence and Drug Encapsulation Properties

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Computational Peptide Science

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2405))

Abstract

Our published studies on the self- and co-assembly of cyclo-HH peptides demonstrated their capacity to coordinate with Zn(II), their enhanced photoluminescence and their ability to self-encapsulate epirubicin, a chemotherapy drug. Here, we provide a detailed description of computational and experimental methodology for the study of cyclo-HH self- and co-assembling mechanisms, photoluminescence, and drug encapsulation properties. We outline the experimental protocols, which involve fluorescence spectroscopy, transmission electron microscopy, and atomic force microscopy protocols, as well as the computational protocols, which involve structural and energetic analysis of the assembled nanostructures. We suggest that the computational and experimental methods presented here can be generalizable, and thus can be applied in the investigation of self- and co-assembly systems involving other short peptides, encapsulating compounds and binding to ions, beyond the particular ones presented here.

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References

  1. Wang H, Feng Z, Xu B (2017) Bioinspired assembly of small molecules in cell milieu. Chem Soc Rev 46:2421–2436

    Article  CAS  Google Scholar 

  2. Wei G, Su Z, Reynolds NP, Arosio P, Hamley IW, Gazit E, Mezzenga R (2017) Self-assembling peptide and protein amyloids: from structure to tailored function in nanotechnology. Chem Soc Rev 46:4661–4708

    Article  CAS  Google Scholar 

  3. DeGrado WF, Wasserman ZR, Lear JD (1989) Protein design, a minimalist approach. Science 243:622–628

    Article  CAS  Google Scholar 

  4. Reches M, Gazit E (2003) Casting metal nanowires within discrete self-assembled peptide nanotubes. Science 300:625–627

    Article  CAS  Google Scholar 

  5. Gazit E (2007) Self assembly of short aromatic peptides into amyloid fibrils and related nanostructures. Prion 1:32–35

    Article  Google Scholar 

  6. Yemini M, Reches M, Gazit E, Rishpon J (2005) Peptide nanotube-modified electrodes for enzyme-biosensor applications. Anal Chem 77:5155–5159

    Article  CAS  Google Scholar 

  7. Handelman A, Kuritz N, Natan A, Rosenman G (2016) Reconstructive phase transition in ultrashort peptide nanostructures and induced visible photoluminescence. Langmuir 32:2847–2862

    Article  CAS  Google Scholar 

  8. Guo C, Arnon ZA, Qi R, Zhang Q, Adler-Abramovich L, Gazit E, Wei G (2016) Expanding the nanoarchitectural diversity through aromatic di- and tri-peptide coassembly: nanostructures and molecular mechanisms. ACS Nano 10:8316–8324

    Article  CAS  Google Scholar 

  9. Nikitin T, Kopyl S, Shur VY, Kopelevich YV, Kholkin AL (2016) Low-temperature photoluminescence in self-assembled diphenylalanine microtubes. Phys Lett A 380:1658–1662

    Article  CAS  Google Scholar 

  10. Guo C, Luo Y, Zhou R, Wei G (2014) Triphenylalanine peptides self-assemble into nanospheres and nanorods that are different from the nanovesicles and nanotubes formed by diphenylalanine peptides. Nanoscale 6:2800–2811

    Article  CAS  Google Scholar 

  11. Tao K, Fan Z, Sun L, Makam P, Tian Z, Ruegsegger M, Shaham-Niv S, Hansford D, Aizen R, Pan Z, Galster S, Ma J, Yuan F, Si M, Qu S, Zhang M, Gazit E, Li J (2018) Quantum confined peptide assemblies with tunable visible to near-infrared spectral range. Nat Commun 9:3217

    Article  Google Scholar 

  12. Barondeau DP, Kassmann CJ, Tainer JA, Getzoff ED (2002) Structural chemistry of a green fluorescent protein Zn biosensor. J Am Chem Soc 124:3522–3524

    Article  CAS  Google Scholar 

  13. Tao K, Chen Y, Orr AA, Tian Z, Makam P, Gilead S, Si M, Rencus-Lazar S, Qu S, Zhang M, Tamamis P, Gazit E (2020) Enhanced fluorescence for bioassembly by environment-switching doping of metal ions. Adv Funct Mater 30:1909614

    Article  CAS  Google Scholar 

  14. Chen Y, Orr AA, Tao K, Wang Z, Ruggiero A, Shimon LJW, Schnaider L, Goodall A, Rencus-Lazar S, Gilead S, Slutsky I, Tamamis P, Tan Z, Gazit E (2020) High-efficiency fluorescence through bioinspired supramolecular self-assembly. ACS Nano 14:2798–2807

    Article  CAS  Google Scholar 

  15. Brooks BR, Brooks CL, Mackerell AD, Nilsson L, Petrella RJ, Roux B, Won Y, Archontis G, Bartels C, Boresch S, Caflisch A, Caves L, Cui Q, Dinner AR, Feig M, Fischer S, Gao J, Hodoscek M, Im W, Kuczera K, Lazaridis T, Ma J, Ovchinnikov V, Paci E, Pastor RW, Post CB, Pu JZ, Schaefer M, Tidor B, Venable RM, Woodcock HL, Wu X, Yang W, York DM, Karplus M (2009) CHARMM: the biomolecular simulation program. J Comput Chem 30:1545–1614

    Article  CAS  Google Scholar 

  16. Humphrey W, Dalke A, Schulten K (1996) VMD: visual molecular dynamics. J Mol Graph 14(33-8):27–28

    Google Scholar 

  17. Sterling T, Irwin JJ (2015) ZINC 15--ligand discovery for everyone. J Chem Inf Model 55:2324–2337

    Article  CAS  Google Scholar 

  18. Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, Li Q, Shoemaker BA, Thiessen PA, Yu B, Zaslavsky L, Zhang J, Bolton EE (2019) PubChem 2019 update: improved access to chemical data. Nucleic Acids Res 47:D1102–D1109

    Article  Google Scholar 

  19. ChemAxon (n.d.) ChemAxon MarvinSketch. Version 17.1.30. http://www.chemaxon.com. Accessed 18 Dec 2020

  20. Lin F-Y, Huang J, Pandey P, Rupakheti C, Li J, Roux BT, MacKerell AD (2020) Further optimization and validation of the classical drude polarizable protein force field. J Chem Theory Comput 16:3221–3239

    Article  CAS  Google Scholar 

  21. Tamamis P, Kasotakis E, Archontis G, Mitraki A (2014) Combination of theoretical and experimental approaches for the design and study of fibril-forming peptides. Methods Mol Biol 1216:53–70

    Article  CAS  Google Scholar 

  22. Lee J, Cheng X, Swails JM, Yeom MS, Eastman PK, Lemkul JA, Wei S, Buckner J, Jeong JC, Qi Y, Jo S, Pande VS, Case DA, Brooks CL, MacKerell AD, Klauda JB, Im W (2016) CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM Simulations Using the CHARMM36 Additive Force Field. J Chem Theory Comput 12:405–413

    Article  CAS  Google Scholar 

  23. Jo S, Kim T, Iyer VG, Im W (2008) CHARMM-GUI: a web-based graphical user interface for CHARMM. J Comput Chem 29:1859–1865

    Article  CAS  Google Scholar 

  24. Mayer SW (1963) A molecular parameter relationship between surface tension and liquid compressibility. J Phys Chem 67:2160–2164

    Article  CAS  Google Scholar 

  25. Tang KE, Bloomfield VA (2000) Excluded volume in solvation: sensitivity of scaled-particle theory to solvent size and density. Biophys J 79:2222–2234

    Article  CAS  Google Scholar 

  26. Seeber M, Cecchini M, Rao F, Settanni G, Caflisch A (2007) Wordom: a program for efficient analysis of molecular dynamics simulations. Bioinformatics 23(19):2625–2627

    Article  CAS  Google Scholar 

  27. Seeber M, Felline A, Raimondi F, Muff S, Friedman R, Rao F, Caflisch A, Fanelli F (2011) Wordom: a user-friendly program for the analysis of molecular structures, trajectories, and free energy surfaces. J Comput Chem 32:1183–1194

    Article  CAS  Google Scholar 

  28. Gohlke H, Case DA (2004) Converging free energy estimates: MM-PB(GB)SA studies on the protein-protein complex Ras-Raf. J Comput Chem 25:238–250

    Article  CAS  Google Scholar 

  29. Hayes JM, Archontis G (2012) MM-GB(PB)SA calculations of protein-ligand binding free energies. Molecular dynamics - studies of synthetic and biological macromolecules

    Google Scholar 

  30. Im W, Lee MS, Brooks CL (2003) Generalized born model with a simple smoothing function. J Comput Chem 24:1691–1702

    Article  CAS  Google Scholar 

  31. Wohlfarth C (2015) Static dielectric constants of pure liquids and binary liquid mixtures: supplement to volume IV/17

    Google Scholar 

  32. Khimenko MT, Litinskaya VV, Khomenko GP (1982) Effect of concentration on the polarizability of isopropyl alcohol in dimethyl sulfoxide. Zh Fiz Khim 56:867–870

    CAS  Google Scholar 

  33. Zhang J, Zhang H, Wu T, Wang Q, van der Spoel D (2017) Comparison of implicit and explicit solvent models for the calculation of solvation free energy in organic solvents. J Chem Theory Comput 13:1034–1043

    Article  CAS  Google Scholar 

  34. Kumar A, Yoluk O, MacKerell AD (2020) FFParam: Standalone package for CHARMM additive and Drude polarizable force field parametrization of small molecules. J Comput Chem 41:958–970

    Article  CAS  Google Scholar 

  35. Vanommeslaeghe K, MacKerell AD (2012) Automation of the CHARMM General Force Field (CGenFF) I: bond perception and atom typing. J Chem Inf Model 52:3144–3154

    Article  CAS  Google Scholar 

  36. Vanommeslaeghe K, Raman EP, MacKerell AD (2012) Automation of the CHARMM General Force Field (CGenFF) II: assignment of bonded parameters and partial atomic charges. J Chem Inf Model 52:3155–3168

    Article  CAS  Google Scholar 

  37. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR et al (2016) Gaussian 03. Gaussian, Inc., Wallingford, CT

    Google Scholar 

  38. Parrish RM, Burns LA, Smith DGA, Simmonett AC, DePrince AE, Hohenstein EG, Bozkaya U, Sokolov AY, Di Remigio R, Richard RM, Gonthier JF, James AM, McAlexander HR, Kumar A, Saitow M, Wang X, Pritchard BP, Verma P, Schaefer HF, Patkowski K, King RA, Valeev EF, Evangelista FA, Turney JM, Crawford TD, Sherrill CD (2017) Psi4 1.1: an open-source electronic structure program emphasizing automation, advanced libraries, and interoperability. J Chem Theory Comput 13:3185–3197

    Article  CAS  Google Scholar 

  39. Grossfield A, Zuckerman DM (2009) Quantifying uncertainty and sampling quality in biomolecular simulations. Annu Rep Comput Chem 5:23–48

    Article  CAS  Google Scholar 

Download references

Acknowledgments

A.A.O acknowledges the Texas A&M University Graduate Diversity Fellowship from the Texas A&M University Graduate and Professional School. All MD simulations and computational analysis were conducted using the Ada supercomputing cluster at the Texas A&M High Performance Research Computing Facility, and additional facilities at Texas A&M University. E.G. acknowledges the support part by the European Research Council under the European Union Horizon 2020 research and innovation program (No. 694426). E.G. also acknowledges support from NSF-BSF Joint Funding Research Grants (No. 2020752). Y.C. gratefully acknowledges the Center for Nanoscience and Nanotechnology of Tel Aviv University for financial support. PT acknowledges support from the National Science Foundation (Award Number 2104558; NSF-BSF: Computational and Experimental Design of Novel Peptide Nanocarriers for Cancer Drugs).

Author information

Author notes

  1. Asuka A. Orr and Yu Chen contributed equally to this work.

Authors and Affiliations

  1. Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, USA

    Asuka A. Orr & Phanourios Tamamis

  2. Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

    Yu Chen & Ehud Gazit

  3. Department of Materials Science and Engineering, Texas A&M University, College Station, TX, USA

    Phanourios Tamamis

Authors
  1. Asuka A. Orr
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  2. Yu Chen
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  3. Ehud Gazit
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  4. Phanourios Tamamis
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Corresponding author

Correspondence to Phanourios Tamamis .

Editor information

Editors and Affiliations

  1. Lab de Biologie Structurale de la Cellule (CNRS UMR7654), Ecole Polytechnique, Palaiseau, France

    Thomas Simonson

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Orr, A.A., Chen, Y., Gazit, E., Tamamis, P. (2022). Computational and Experimental Protocols to Study Cyclo-dihistidine Self- and Co-assembly: Minimalistic Bio-assemblies with Enhanced Fluorescence and Drug Encapsulation Properties. In: Simonson, T. (eds) Computational Peptide Science. Methods in Molecular Biology, vol 2405. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1855-4_10

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  • DOI: https://doi.org/10.1007/978-1-0716-1855-4_10

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1854-7

  • Online ISBN: 978-1-0716-1855-4

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