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Reactivity of amino acids and short peptide sequences: identifying bioactive compounds via DFT calculations

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Abstract

Bioactive peptides are short amino acid sequences that play important roles in various physiological processes, including antioxidant and protective effects. These compounds can be obtained through protein hydrolysis and have a wide range of potential applications in a variety of areas. However, despite the potential of these compounds, more in-depth knowledge is still necessary to better understand details regarding their chemical reactivity and electronic properties. In this study, we used molecular modeling techniques to investigate the electronic structure of isolated amino acids (AA) and short peptide sequences. Details on the relative alignments between the frontier electronic levels, local chemical reactivity and donor–acceptor properties of the 20 primary amino acids and some di- and tripeptides were evaluated in the framework of the density functional theory (DFT). Our results suggest that the electronic properties of isolated amino acids can be used to interpret the reactivity of short sequences. We found that aromatic and charged amino acids, as well as Methionine, play a key role in determining the local reactivity of peptides, in agreement with experimental data. Our analyses also allowed us to identify the influence of the relative position of AA and terminations on the local reactivity of the sequences, which can guide experimental studies and help to propose/evaluate possible mechanisms of action. In summary, our data indicate that the position of active sites of polypeptides can be predicted from short sequences, providing a promising strategy for the synthesis and bioprospection of new optimized compounds.

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Acknowledgements

The authors thank the Brazilian National Council for Scientific and Technological Development (CNPq) (Grants 448310/2014-7, 420449/2018-3 and 428211/2018-6) and Coordination for the Improvement of Higher Education (CAPES) (grant 88887.508044/2020-00) for the financial support. This research was also supported by resources supplied by the Center for Scientific Computing (NCC/Grid-UNESP) of the São Paulo State University (UNESP) and CENAPAD/SP.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, EBB-MP, São Paulo State University (UNESP), Araraquara, SP, Brazil

    Daiane F. Oliveira

  2. School of Sciences, POSMAT, São Paulo State University (UNESP), Bauru, SP, Brazil

    Alex P. Coleone

  3. Federal Institute of Education, Science and Technology of São Paulo (IFSP), Matão, SP, Brazil

    Filipe C. D. A. Lima

  4. Institute of Sciences and Engineering, São Paulo State University (UNESP), Itapeva, SP, Brazil

    Augusto Batagin-Neto

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  1. Daiane F. Oliveira
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Contributions

Conceptualization: DO, FL, AB-N; Methodology: FL, AB-N; Formal analysis and investigation: DO, AC; Writing—original draft preparation: DO, AC; Writing—review and editing: FL, AB-N; Funding acquisition: AB-N; Resources: FL, AB-N; Supervision: FL, AB-N.

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Correspondence to Augusto Batagin-Neto.

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Oliveira, D.F., Coleone, A.P., Lima, F.C.D.A. et al. Reactivity of amino acids and short peptide sequences: identifying bioactive compounds via DFT calculations. Mol Divers (2024). https://doi.org/10.1007/s11030-024-10868-y

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