Reliable values of the solid-state NMR (SSNMR) parameters together with precise structural data specific for a given amino acid site in an oligopeptide are needed for the proper interpretation of measurements aiming at an understanding of oligopeptides' function. The periodic density functional theory (DFT)-based computations of geometries and SSNMR chemical shielding tensors (CSTs) of solids are shown to be accurate enough to support the SSNMR investigations of suitably chosen models of oriented samples of oligopeptides. This finding is based on a thorough comparison between the DFT and experimental data for a set of tripeptides with both 13Cα and 15Namid CSTs available from the single-crystal SSNMR measurements and covering the three most common secondary structural elements of polypeptides. Thus, the ground is laid for a quantitative description of local spectral parameters of crystalline oligopeptides, as demonstrated for the backbone 15Namid nuclei of samarosporin I, which is a pentadecapeptide (composed of five classical and ten nonproteinogenic amino acids) featuring a strong antimicrobial activity.

Institute of Macromolecular Chemistry Czech Academy of Sciences Heyrovsky Square 2 16206 Prague Czech Republic

Zobrazit více v PubMed

Hamley I.W. Small Bioactive Peptides for Biomaterials Design and Therapeutics. Chem. Rev. 2017;117:14015–14041. doi: 10.1021/acs.chemrev.7b00522. PubMed DOI

Wang J., Dou X., Song J., Lyu Y., Zhu X., Xu L., Li W., Shan A. Antimicrobial peptides: Promising alternatives in the post feeding antibiotic era. Med. Res. Rev. 2019;39:831–859. doi: 10.1002/med.21542. PubMed DOI

Yount N.Y., Weaver D.C., Lee E.Y., Lee M.W., Wang H., Chan L.C., Wong G.C.L., Yeaman M.R. Unifying structural signature of eukaryotic α-helical host defense peptides. Proc. Natl. Acad. Sci. USA. 2019;116:6944–6953. doi: 10.1073/pnas.1819250116. PubMed DOI PMC

Du L., Risinger A.L., Mitchell C.A., You J., Stamps B.W., Pan N., King J.B., Bopassa J.C., Judge S.I.V., Yang Z., et al. Unique amalgamation of primary and secondary structural elements transform peptaibols into potent bioactive cell-penetrating peptides. Proc. Natl. Acad. Sci. USA. 2017;114:8957–8966. doi: 10.1073/pnas.1707565114. PubMed DOI PMC

Raheem N., Straus S.K. Mechanisms of Action for Antimicrobial Peptides with Antibacterial and Antibiofilm Functions. Front. Microbiol. 2019;10:2866. doi: 10.3389/fmicb.2019.02866. PubMed DOI PMC

Molugu T.R., Lee S., Brown M.F. Concepts and Methods of Solid-State NMR Spectroscopy Applied to Biomembranes. Chem. Rev. 2017;117:12087–12132. doi: 10.1021/acs.chemrev.6b00619. PubMed DOI

Salnikov E., Bertani P., Raap J., Bechinger B. Analysis of the amide 15N chemical shift tensor of the Cα tetrasubstituted constituent of membrane-active peptaibols, the α-aminoisobutyric acid residue, compared to those of di- and tri-substituted proteinogenic amino acid residues. J. Biomol. NMR. 2009;45:373–387. doi: 10.1007/s10858-009-9380-5. PubMed DOI

Nagao T., Mishima D., Javkhlantugs N., Wang J., Ishioka D., Yokota K., Norisada K., Kawamura I., Ueda K., Naito A. Structure and orientation of antibiotic peptide alamethicin in phospholipid bilayers as revealed by chemical shift oscillation analysis of solid state nuclear magnetic resonance and molecular dynamics simulation. BBA Biomembr. 2015;1848:2789–2798. doi: 10.1016/j.bbamem.2015.07.019. PubMed DOI

Grage S.L., Kara S., Bordessa A., Doan V., Rizzolo F., Putzu M., Kubař T., Papini A.M., Chaume G., Brigaud T., et al. Orthogonal 19F-Labeling for Solid-State NMR Spectroscopy Reveals the Conformation and Orientation of Short Peptaibols in Membranes. Chem. Eur. J. 2018;24:4238–4335. doi: 10.1002/chem.201704307. PubMed DOI

Bonhomme C., Gervais C., Babonneau F., Coelho C., Pourpoint F., Azais T., Asbrook S.E., Griffin J.M., Yates J.R., Pickard J.C. First-Principles Calculation of NMR Parameters Using the Gauge Including Projector Augmented Wave Method: A Chemist’s Point of View. Chem. Rev. 2012;112:5733–5779. doi: 10.1021/cr300108a. PubMed DOI

Czernek J., Brus J. Theoretical Investigations Into the Variability of the N-15 Solid-State NMR Parameters Within an Antimicrobial Peptide Ampullosporin A. Phys. Res. 2018;67:S349–S356. doi: 10.33549/physiolres.933976. PubMed DOI

Chekmenev E.Y., Xu R.Z., Mashuta M.S., Wittebort R.J. Glycyl C alpha chemical shielding in tripeptides: Measurement by solid-state NMR and correlation with X-ray structure and theory. J. Am. Chem. Soc. 2002;124:11894–11899. doi: 10.1021/ja026700g. PubMed DOI

Chekmenev E.Y., Zhang Q.W., Waddell K.W., Mashuta M.S., Wittebort R.J. N-15 chemical shielding in glycyl tripeptides: Measurement by solid-state NMR and correlation with x-ray structure. J. Am. Chem. Soc. 2004;126:379–384. doi: 10.1021/ja0370342. PubMed DOI

Waddell K.W., Chekmenev E.Y., Wittebort R.J. Single-Crystal Studies of Peptide Prolyl and Glycyl 15N Shielding Tensors. J. Am. Chem. Soc. 2005;127:9030–9035. doi: 10.1021/ja044204h. PubMed DOI

Kang X., Elso C., Penfield J., Kirui A., Chen A., Zhang L., Wang T. Integrated solid-state NMR and molecular dynamics modeling determines membrane insertion of human β-defensin analog. Commun. Biol. 2019;2:402–410. doi: 10.1038/s42003-019-0653-6. PubMed DOI PMC

Gessmann R., Axford D., Evans G., Bruckner H., Petratos K. The crystal structure of samarosporin I at atomic resolution. J. Pept. Sci. 2012;18:678–684. doi: 10.1002/psc.2454. PubMed DOI

Strohmeier M., Grant D.M. Experimental and theoretical investigation of the C-13 and N-15 chemical shift tensors in melanostatin-exploring the chemical shift tensor as a structural probe. J. Am. Chem. Soc. 2004;126:966–977. doi: 10.1021/ja037330e. PubMed DOI

Nerli S., McShan A.C., Sgourakis N.G. Chemical shift-based methods in NMR structure determination. Prog. Nucl. Mag. Res. Sp. 2018;106:1–25. doi: 10.1016/j.pnmrs.2018.03.002. PubMed DOI PMC

Harris R.K., Wasylishen R.E., Duer M.J., editors. NMR Crystallography. Wiley; Chichester, UK: 2009.

Hofstetter A., Balodis M., Paruzzo F.M., Widdifield C.M., Stevanato G., Pinon A.C., Bygrave P.J., Day G.M., Emsley L. Rapid structure determination of molecular solids using chemical shifts directed by unambiguous prior constraints. J. Am. Chem. Soc. 2019;141:16624–16634. doi: 10.1021/jacs.9b03908. PubMed DOI PMC

Guzmán-Afonso C., Hong Y., Colaux H., Iijima H., Saitow A., Fukumura T., Aoyama Y., Motoki S., Oikawa T., Yamazaki T., et al. Understanding hydrogen-bonding structures of molecular crystals via electron and NMR nanocrystallography. Nat. Commun. 2019;10:1–10. doi: 10.1038/s41467-019-11469-2. PubMed DOI PMC

Awosanya E.O., Lapin J., Nevzorov A.A. NMR “crystallography” for uniformly (13C, 15N)-labeled oriented membrane proteins. Angew. Chem. Int. Ed. 2020;59:3554–3557. doi: 10.1002/anie.201915110. PubMed DOI

Czernek J., Urbanová M., Brus J. NMR crystallography of the polymorphs of metergoline. Crystals. 2018;8:378. doi: 10.3390/cryst8100378. DOI

Sternberg U., Witter R. Investigation of backbone dynamics and local geometry of bio-molecules using calculated NMR chemical shifts and anisotropies. J. Biomol. NMR. 2019;73:727–741. doi: 10.1007/s10858-019-00284-y. PubMed DOI

Narwani T.J., Santuz H., Shinada N., Vattekatte A.M., Ghouzam Y., Srinivasan N., Gelly J.-C., de Brevern A.G. Recent advances on polyproline II. Amino Acids. 2017;49:705–713. doi: 10.1007/s00726-017-2385-6. PubMed DOI

Czernek J., Pawlak T., Potrzebowski M.J., Brus J. The comparison of approaches to the solid-state NMR-based structural refinement of vitamin B1 hydrochloride and of its monohydrate. Chem. Phys. Lett. 2013;555:135–140. doi: 10.1016/j.cplett.2012.11.002. DOI

Perrin B.S., Pastor R.W., Cotton M. Combining NMR Spectroscopic Measurements and Molecular Dynamics Simulations to Determine the Orientation of Amphipathic Peptides in Lipid Bilayers. In: Separovic S., Naito A., editors. Advances in Biological Solid-State NMR: Proteins and Membrane-Active Peptides. 1st ed. Royal Society of Chemistry; London, UK: 2014.

Witanowski M., Stefaniak L., Szymański S., Januszewski H. External neat nitromethane scale for nitrogen chemical shifts. J. Magn. Reson. 1977;28:217–226. doi: 10.1016/0022-2364(77)90148-2. DOI

Alderman D.W., Sherwood M.H., Grant D.M. Comparing, modeling and assigning chemical-shift tensors in the cartesian, irreducible spherical, and icosahedral representations. J. Magn. Reson. A. 1993;101:188–197. doi: 10.1006/jmra.1993.1029. DOI

Czernek J., Brus J. Theoretical predictions of the two-dimensional solid-state NMR spectra: A case study of the 13C—1H correlations in metergoline. Chem. Phys. Lett. 2013;586:56–60. doi: 10.1016/j.cplett.2013.09.015. DOI

Czernek J., Brus J. The covariance of the differences between experimental and theoretical chemical shifts as an aid for assigning two-dimensional heteronuclear correlation solid-state NMR spectra. Chem. Phys. Lett. 2014;608:334–339. doi: 10.1016/j.cplett.2014.05.099. DOI

Czernek J., Brus J. Exploring accuracy limits of predictions of the 1-H chemical shielding anisotropy in the solid state. Molecules. 2019;24:1731. doi: 10.3390/molecules24091731. PubMed DOI PMC

Ramon-Martín F., Annaval T., Buchoux S., Sarazin C., D’Amelio N. ADAPTABLE: A comprehensive web platform of antimicrobial peptides tailored to the user’s research. Life Sci. Alliance. 2020;2:e201900512. doi: 10.26508/lsa.201900512. PubMed DOI PMC

Chu K.T., Wang H.X., Ng T.B. Fungal Peptides with Antifungal Activity. In: Kastin A.J., editor. Handbook of Biologically Active Peptides. 1st ed. Academic Press; Cambridge, MA, USA: 2006.

Wel van der P.C.A. New applications of solid-state NMR in structural biology. Emerg. Top. Life Sci. 2018;2:57–67. doi: 10.1042/ETLS20170088. PubMed DOI PMC

Marassi F.M., Opella S.J. A Solid-State NMR Index of Helical Membrane Protein Structure and Topology. J. Magn. Reson. 2000;144:150–155. doi: 10.1006/jmre.2000.2035. PubMed DOI PMC

Salnikov E.S., Aisenbrey C., Pokrandt B., Brügger B., Bechinger B. Structure, Topology, and Dynamics of Membrane-Inserted Polypeptides and Lipids by Solid-State NMR Spectroscopy: Investigations of the Transmembrane Domains of the DQ Beta-1 Subunit of the MHC II Receptor and of the COP I Protein. Front. Mol. Biosci. 2019;6:83. doi: 10.3389/fmolb.2019.00083. PubMed DOI PMC

Salnikov E.S., Friedrich H., Li X., Bertani P., Reissmann S., Hertweck C., O’Neil J.D.J., Raap J., Bechinger B. Structure and Alignment of the Membrane-Associated Peptaibols Ampullosporin A and Alamethicin by Oriented 15N and 31P Solid-State NMR Spectroscopy. Biophys. J. 2009;96:86–100. doi: 10.1529/biophysj.108.136242. PubMed DOI PMC

Yarava J.R., Nishiyama Y., Raghothama S., Ramanathan V.K. Conformational investigation of peptides using solid-state NMR spectroscopy–A study of polymorphism of β-turn peptides containing diprolines. Chem. Biol. Drug Des. 2020;95:394–407. doi: 10.1111/cbdd.13649. PubMed DOI

Kresse G., Joubert D. From ultrasoft pseudopotentials to the projector augmented-wave method. Phys. Rev. B. 1999;59:1758–1775. doi: 10.1103/PhysRevB.59.1758. DOI

Segall M.D., Lindan P.J.D., Probert M.J., Pickard C.J., Hasnip P.J., Clark S.J., Payne M.C. First principles simulation: Ideas, illustrations, and the CASTEP code. J. Phys. Condens. Matter. 2002;14:2717–2744. doi: 10.1088/0953-8984/14/11/301. DOI

Clark S.J., Segall M.D., Pickard C.J., Hasnip P.J., Probert M.J., Refson K., Payne M.C. First principles methods using CASTEP. Z. Krist. Cryst. Mater. 2005;220:567–570. doi: 10.1524/zkri.220.5.567.65075. DOI

Perdew J.P., Burke K., Ernzerhof M. Generalized gradient approximation made simple. Phys. Rev. Lett. 1996;77:3865–3868. doi: 10.1103/PhysRevLett.77.3865. PubMed DOI

Pickard C.J., Mauri F. All-electron magnetic response with pseudopotentials: NMR chemical shifts. Phys. Rev. B. 2001;63:245101. doi: 10.1103/PhysRevB.63.245101. DOI

Yates J.R., Pickard C.J., Mauri F. Calculations of NMR chemical shifts for extended systems using ultrasoft pseudopotentials. Phys. Rev. B. 2007;76:024401. doi: 10.1103/PhysRevB.76.024401. DOI

Czernek J., Brus J. On the predictions of the B-11 solid state NMR parameters. Chem. Phys. Lett. 2016;655:66–70. doi: 10.1016/j.cplett.2016.05.027. DOI

Modeling the Structure of Crystalline Alamethicin and Its NMR Chemical Shift Tensors

Parametrizing the Spatial Dependence of 1H NMR Chemical Shifts in π-Stacked Molecular Fragments

Polymorphic Forms of Valinomycin Investigated by NMR Crystallography