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DFT investigation on the structural and vibrational behaviours of the non-protein amino acids in hybrid explicit/continuum solvent: a case of the zwitterions γ-aminobutyric and α − aminoisobutyric acids

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Abstract

Background

The influence of hybrid solvation models on the molecular structures and vibrational characteristics of g−aminobutyric acid (GABA) and a−aminoisobutyric acid (AIB) zwitterions was assessed by employing a variety of Density Functional Theory (DFT). The quantum chemical methods included the B3LYP and B3PW91 hybrid functionals and the 6‑311++G(d,p) basis set.

Methods

The most stable conformation derived from the potential energy surface (PES) scans using the B3LYP/6-311++G(d,p) model chemistry for each studied molecule was predicted within a continuum environment represented by the COSMO and SMD solvation models. The stable structures were subsequently immersed in explicit/COSMO and explicit/SMD hybrid solvation models, where 10 and 8 water molecules were explicitly positioned around the functional groups of the GABA and AIB zwitterions, respectively. The number of water molecules chosen was sufficient to prevent proton transfer among the carboxylate group (COO−) and the ammonium group (NH3+) within each molecule under investigation. After optimizing the geometry of each hydrated complex, the normal vibrational modes were determined. The scaled theoretical frequencies obtained from the various model chemistries were then compared to available experimental data from infrared (IR) and Raman spectroscopy.

Results

In the case of GABA and AIB molecules, the comparisons revealed that the B3LYP/6-311++G(d,p) model chemistry yielded wavenumber values that closely matched the experimental IR and Raman data, particularly when the explicit/SMD solvent was employed. The computed results indicate deviations of less than 4% when compared to the experimental data for the two molecules under investigation.

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Data availability

The data presented in this study are available upon request from the corresponding authors.

References

  1. Ding Y, Ting JP, Liu J et al (2020) Impact of non-proteinogenic amino acids in the discovery and development of peptide therapeutics. Amino Acids 52:1207–1226. https://doi.org/10.1007/s00726-020-02890-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Goettig P, Koch NG, Budisa N (2023) Non-canonical amino acids in analyses of protease structure and function. Int J Mol Sci 24:14035. https://doi.org/10.3390/ijms241814035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sarasa SB, Mahendran R, Muthusamy G et al (2020) A brief review on the non-protein amino acid, gamma-amino butyric acid (gaba): its production and role in microbes. Curr Microbiol 77:534–544. https://doi.org/10.1007/s00284-019-01839-w

    Article  CAS  PubMed  Google Scholar 

  4. Al-Wadei HAN, Ullah MF, Al-Wadei M (2011) GABA (γ-aminobutyric acid), a non-protein amino acid counters the β-adrenergic cascade-activated oncogenic signaling in pancreatic cancer: A review of experimental evidence. Mol Nutr Food Res 55:1745–1758. https://doi.org/10.1002/mnfr.201100229

    Article  CAS  PubMed  Google Scholar 

  5. Alonso JL, Peña I, López JC et al (2019) The shape of the simplest non-proteinogenic Amino Acid α-Aminoisobutyric Acid (Aib). Chem – A Eur J 25:2288–2294. https://doi.org/10.1002/chem.201805038

    Article  CAS  Google Scholar 

  6. Kinnersley AM, Turano FJ (2000) Gamma aminobutyric acid (GABA) and plant responses to stress. CRC Crit Rev Plant Sci 19:479–509. https://doi.org/10.1080/07352680091139277

    Article  CAS  Google Scholar 

  7. Dhakal R, Bajpai VK, Baek K-H (2012) Production of gaba (γ - aminobutyric acid) by microorganisms: a review. Brazilian J Microbiol 43:1230–1241. https://doi.org/10.1590/S1517-83822012000400001

    Article  CAS  Google Scholar 

  8. Brosnan JT, Brosnan ME (2013) Glutamate: a truly functional amino acid. Amino Acids 45:413–418. https://doi.org/10.1007/s00726-012-1280-4

    Article  CAS  PubMed  Google Scholar 

  9. Tsuji G, Misawa T, Doi M, Demizu Y (2018) Extent of helical induction caused by introducing α-aminoisobutyric acid into an oligovaline sequence. ACS Omega 3:6395–6399. https://doi.org/10.1021/acsomega.8b01030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dou Z, Li M, Shen Z et al (2023) GAD1-mediated GABA elicits aggressive characteristics of human oral cancer cells. Biochem Biophys Res Commun 681:80–89. https://doi.org/10.1016/j.bbrc.2023.09.041

    Article  CAS  PubMed  Google Scholar 

  11. Bowery NG, Smart TG (2006) GABA and glycine as neurotransmitters: a brief history. Br J Pharmacol 147:. https://doi.org/10.1038/sj.bjp.0706443

  12. Crittenden DL, Chebib M, Jordan MJT (2005) Stabilization of zwitterions in solution: GABA analogues. J Phys Chem A 109:4195–4201. https://doi.org/10.1021/jp050320a

    Article  CAS  PubMed  Google Scholar 

  13. Sharma B, Chandra A (2018) On the issue of closed versus open forms of gamma-aminobutyric acid (GABA) in water: Ab initio molecular dynamics and metadynamics studies. J Chem Phys 148:. https://doi.org/10.1063/1.5021702

  14. Harris H (1952) Family studies on the urinary excretion of ß-aminoisobutyric acid. Ann Eugen 17:43–49. https://doi.org/10.1111/j.1469-1809.1952.tb02496.x

    Article  Google Scholar 

  15. Crumpler HR, Dent CE, Harris H, Westall RG (1951) β-Aminoisobutyric Acid (α-Methyl-β-Alanine): A New Amino-Acid Obtained from Human Urine. Nature 167:307–308. https://doi.org/10.1038/167307a0

    Article  CAS  PubMed  Google Scholar 

  16. Landi N, Ragucci S, Di Maro A (2021) Amino acid composition of milk from cow, sheep and goat raised in ailano and valle agricola, two localities of ‘alto casertano’ (campania region). Foods 10:2431. https://doi.org/10.3390/foods10102431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Purvis GD, King JW (1988) Proton transfer and triol formation in the simulation ofGABA solvation. Int J Quantum Chem 34:593–600. https://doi.org/10.1002/qua.560340863

    Article  Google Scholar 

  18. Suresh DM, Sajan D, Laladas KP et al (2008) Vibrational Spectra of γ-Aminobutyric Acid. In: AIP Conference Proceedings. AIP, pp 95–97

  19. Koyambo-Konzapa S-J, Premkumar R, Berthelot Saïd Duvalier RV et al (2022) Electronic, spectroscopic, molecular docking and molecular dynamics studies of neutral and zwitterionic forms of 3, 4-dihydroxy-l-phenylalanine: A novel lung cancer drug. J Mol Struct 1260:132844. https://doi.org/10.1016/j.molstruc.2022.132844

    Article  CAS  Google Scholar 

  20. Minguirbara A, Vamhindi BSDR, Koyambo-Konzapa SJ, Nsangou M (2020) Effects of counterions and solvents on the geometrical and vibrational features of dinucleoside-monophosphate (dNMP): case of 3’,5’-dideoxycytidine-monophosphate (dDCMP). J Mol Model 26:. https://doi.org/10.1007/s00894-020-04369-6

  21. Koyambo-Konzapa S-J, Dhaouadi Z, Nsangou M (2019) Hydration of l-glycylvaline and l-glycylvalylglycine zwitterions: Structural and vibrational studies using DFT method. J Mol Graph Model 88:194–202. https://doi.org/10.1016/j.jmgm.2019.01.012

    Article  CAS  PubMed  Google Scholar 

  22. Koyambo-Konzapa SJ, Minguirbara A, Nsangou M (2015) Solvent effects on the structures and vibrational features of zwitterionic dipeptides: L-diglycine and L-dialanine. J Mol Model 21:. https://doi.org/10.1007/s00894-015-2718-x

  23. Daver H, Algarra AG, Rebek J et al (2018) Mixed explicit-implicit solvation approach for modeling of alkane complexation in water-soluble self-assembled capsules. J Am Chem Soc 140:12527–12537. https://doi.org/10.1021/jacs.8b06984

    Article  CAS  PubMed  Google Scholar 

  24. Raucci U, Perrella F, Donati G et al (2020) Ab-initio molecular dynamics and hybrid explicit-implicit solvation model for aqueous and nonaqueous solvents: <scp>GFP</scp> chromophore in water and methanol solution as case study. J Comput Chem 41:2228–2239. https://doi.org/10.1002/jcc.26384

    Article  CAS  PubMed  Google Scholar 

  25. Kamerlin SCL, Haranczyk M, Warshel A (2009) Are Mixed Explicit/Implicit Solvation Models Reliable for Studying Phosphate Hydrolysis? A Comparative Study of Continuum, Explicit and Mixed Solvation Models. ChemPhysChem 10:1125–1134. https://doi.org/10.1002/cphc.200800753

    Article  CAS  PubMed  Google Scholar 

  26. Pallavi L, Tonannavar J, Tonannavar J (2020) DFT zwitterion model for vibrational and electronic structure of unnatural 3-amino-3-(4-fluorophenyl)propionic acid, aided by IR and Raman spectroscopy. J Mol Struct 1211:128085. https://doi.org/10.1016/j.molstruc.2020.128085

    Article  CAS  Google Scholar 

  27. Prabhu MD, TonannavarYenagi J, Kamat V, Tonannavar J (2020) XRD structure and vibrational analysis of DL-β-Leucine, as aided by DFT tetramer model and characterized by NBO, AIM and NCI calculations. J Mol Struct 1218:128495. https://doi.org/10.1016/j.molstruc.2020.128495

    Article  CAS  Google Scholar 

  28. Edwin B, Hubert Joe I (2013) Vibrational spectral analysis of anti-neurodegenerative drug Levodopa: A DFT study. J Mol Struct 1034:119–127. https://doi.org/10.1016/j.molstruc.2012.09.004

    Article  CAS  Google Scholar 

  29. Yalagi S (2022) Study of vibrational spectra of zwitterionic 3-Aminobutanoic acid, as supported by DFT calculations. World J Adv Res Rev 16:1122–1131. https://doi.org/10.30574/wjarr.2022.16.3.1487

    Article  CAS  Google Scholar 

  30. Marenich AV, Cramer CJ, Truhlar DG (2009) Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J Phys Chem B 113:6378–6396. https://doi.org/10.1021/jp810292n

    Article  CAS  PubMed  Google Scholar 

  31. Miguel ELM, Santos CIL, Silva CM, Pliego JR Jr (2016) How accurate is the smd model for predicting free energy barriers for nucleophilic substitution reactions in polar protic and dipolar aprotic solvents? J Braz Chem Soc. https://doi.org/10.5935/0103-5053.20160095

    Article  Google Scholar 

  32. Herbert JM (2021) Dielectric continuum methods for quantum chemistry. WIREs Comput Mol Sci 11:. https://doi.org/10.1002/wcms.1519

  33. Guerard JJ, Arey JS (2013) Critical evaluation of implicit solvent models for predicting aqueous oxidation potentials of neutral organic compounds. J Chem Theory Comput 9:5046–5058. https://doi.org/10.1021/ct4004433

    Article  CAS  PubMed  Google Scholar 

  34. Boys SF, Bernardi F (1970) The calculation of small molecular interactions by the differences of separate total energies. Some procedures with reduced errors. Mol Phys 19:553–566. https://doi.org/10.1080/00268977000101561

    Article  CAS  Google Scholar 

  35. Jensen F (2010) An atomic counterpoise method for estimating inter- and intramolecular basis set superposition errors. J Chem Theory Comput 6:100–106. https://doi.org/10.1021/ct900436f

    Article  CAS  PubMed  Google Scholar 

  36. Gaigeot M-P, Ghomi M (2001) Geometrical and vibrational properties of nucleic acid constituents interacting with explicit water molecules as analyzed by density functional theory calculations. 1. Uracil + n w H 2 O ( n w = 1,...,7). J Phys Chem B 105:5007–5017. https://doi.org/10.1021/jp0040401

    Article  CAS  Google Scholar 

  37. Nagy PI, Erhardt PW (2006) Ab initio study of hydrogen-bond formation between cyclic ethers and selected amino acid side chains. J Phys Chem A 110:13923–13932. https://doi.org/10.1021/jp061113t

    Article  CAS  PubMed  Google Scholar 

  38. Hernández B, Pflüger F, Nsangou M, Ghomi M (2009) Vibrational analysis of amino acids and short peptides in hydrated media. iv. amino acids with hydrophobic side chains: <scp>l</scp> -alanine, <scp>l</scp> -Valine, and <scp>l</scp> -Isoleucine. J Phys Chem B 113:3169–3178. https://doi.org/10.1021/jp809204d

    Article  CAS  PubMed  Google Scholar 

  39. Nsangou M (2011) DFT study of geometrical and vibrational features of small amino acids with polar side chains in hydrated media: L-Threonine and L-Serine. Comput Theor Chem 966:364–374. https://doi.org/10.1016/j.comptc.2011.03.038

    Article  CAS  Google Scholar 

  40. Hernández B, Pflüger F, Adenier A et al (2011) Energy maps, side chain conformational flexibility, and vibrational features of polar amino acids <scp>L</scp> -serine and <scp>L</scp> -threonine in aqueous environment. J Chem Phys 135:. https://doi.org/10.1063/1.3617415

  41. Frisch MJ, Trucks GW, Schlegel HB et al (2010) Gaussian09 Revision D.01, Gaussian Inc. Wallingford CT. Gaussian 09 Revis. C.01

  42. Dennington R, Keith T, Millam J (2009) GaussView, Version 5. Semichem Inc. , Shawnee Mission. KS

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Acknowledgements

S-J K-K conveys appreciation to the Abdus Salam International Centre for Theoretical Physics (ICTP) in Trieste, Italy, for awarding a grant through the 2022 ASESMANET Intra-Africa mobility program, which supported a visit to the School of Physics and Earth Sciences at The Technical University of Kenya, Nairobi. The authors acknowledge the Centre for High Performance Computing (CHPC, Grant number MATS862), South Africa, for providing resources to this research project. We also thank Prof. Mahmoud Ghomi (Université Paris 13, France), for providing us with the homemade program BORNS-PC that was useful for the assignment of the vibrational modes.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Higher Teacher’s Training College, The University of Maroua, P.O. Box 46, Maroua, Cameroon

    Yves Dague, Alain Minguirbara & Mama Nsangou

  2. Laboratoire Matière, Energie et Rayonnement (LAMER), Université de Bangui, P.O. Box 1450, Bangui, Central African Republic

    Stève-Jonathan Koyambo-Konzapa

  3. School of Chemistry and Material Science, The Technical University of Kenya, Nairobi, 52428-00200, Kenya

    Holliness Nose

  4. Department of Physics, Faculty of Sciences, University of Ngaoundere, P.O. Box 454, Ngaoundere, Cameroon

    Mama Nsangou

  5. Materials Modeling Group, School of Physics and Earth Science, The Technical University of Kenya, Nairobi, 52428-00200, Kenya

    George Amolo

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  1. Yves Dague
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Contributions

The contributions of the authors are as follows:

Yves Dague: Conceptualization, Writing – original draft, Data curation, Investigation. Stève-Jonathan Koyambo-Konzapa: Conceptualization, Supervision, Investigation, Writing – review & editing. Nose Holliness: Methodology, software. Alain Minguirbara: Methodology, Resources. George Amolo: Validation, Resources. Mama Nsangou: Supervision, Projet administration, Validation.

Corresponding authors

Correspondence to Stève-Jonathan Koyambo-Konzapa or Mama Nsangou.

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Dague, Y., Koyambo-Konzapa, SJ., Nose, H. et al. DFT investigation on the structural and vibrational behaviours of the non-protein amino acids in hybrid explicit/continuum solvent: a case of the zwitterions γ-aminobutyric and α − aminoisobutyric acids. J Mol Model 30, 17 (2024). https://doi.org/10.1007/s00894-023-05817-9

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