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Investigation of the structural dynamics of a knotted protein and its unknotted analog using molecular dynamics

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Abstract

The role of knots in proteins remains elusive. Some studies suggest an impact on stability; the difficulty in comparing systems to assess this effect, however, has been a significant challenge. In this study, we produced and analyzed molecular dynamic trajectories considering three different temperatures of two variants of ornithine transcarbamylase (OTC), only one of which has a 31 knot, in order to evaluate the relative stability of the two molecules. RMSD showed equilibrated structures for the produced trajectories, and RMSF showed subtle differences in flexibility. In the knot moiety, the knotted protein did not show a great deal of fluctuation at any temperature. For the unknotted protein, the residue GLY243 showed a high fluctuation in the corresponding moiety. The fraction of native contacts (Q) showed a similar profile at all temperatures, with the greatest decrease by 436 K. The investigation of conformational behavior with principal component analysis (PCA) and dynamic cross-correlation map (DCCM) showed that knotted protein is less likely to undergo changes in its conformation under the conditions employed compared to unknotted. PCA data showed that the unknotted protein had greater dispersion in its conformations, which suggests that it has a greater capacity for conformation transitions in response to thermal changes. DCCM graphs comparing the 310 K and 436 K temperatures showed that the knotted protein had less change in its correlation and anti-correlation movements, indicating stability compared to the unknotted.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors acknowledge the physical structure and computational support provided by Universidade Federal da Paraíba (UFPB), the computer resources of Centro Nacional de Processamento de Alto Desempenho em São Paulo (CENAPAD-SP). The English text of this paper has been revised by Sidney Pratt, Canadian, MAT (The Johns Hopkins University), RSAdip—TESL (Cambridge University).

Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES) through the research project Bioinformática Estrutural de Proteínas: Modelos, Algoritmos e Aplicações Biotecnológicas (Edital Biologia Computacional 51/2013, processo AUXPE1375/2014 da CAPES). G.B.R. received support from the Brazilian National Council for Scientific and Technological Development (CNPq grant no. 309761/2017–4).

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Authors and Affiliations

  1. Department of Chemistry, Federal University of Paraíba, Cidade Universitária, Joao Pessoa, PB, 58051-900, Brazil

    José Cícero Alves Silva & Gerd Bruno Rocha

  2. Department of Biotechnology, Federal University of Paraíba, Cidade Universitária, Joao Pessoa, PB, 58051-900, Brazil

    Elton José Ferreira Chaves

  3. Fundamental Department of Chemistry, Federal University of Pernambuco, Cidade Universitária, Recife, PE, 50670-901, Brazil

    Gabriel Aires Urquiza de Carvalho

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  1. José Cícero Alves Silva
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  2. Elton José Ferreira Chaves
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  3. Gabriel Aires Urquiza de Carvalho
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  4. Gerd Bruno Rocha
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José Cícero Alves Silva: wrote the original manuscript, performed research, curation, and data analysis. Elton José Ferreira Chaves: wrote the original manuscript, curation and data analysis. Gabriel Aires Urquiza de Carvalho: coordinator and revised the original manuscript. Gerd Bruno Rocha: coordinator, planned the research, fundraising, revised the original manuscript. All the authors have read and approved the final manuscript.

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Correspondence to Gerd Bruno Rocha.

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Silva, J.C.A., Chaves, E.J.F., de Carvalho, G.A.U. et al. Investigation of the structural dynamics of a knotted protein and its unknotted analog using molecular dynamics. J Mol Model 28, 108 (2022). https://doi.org/10.1007/s00894-022-05094-y

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