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Comparative modelling unravels the structural features of eukaryotic TCTP implicated in its multifunctional properties: an in silico approach

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Abstract

Comparative modelling helps compare the structure and functions of a given protein, to track the path of its origin and evolution and also guide in structure-based drug discovery. Presently, this has been applied for modelling the tertiary structure of highly conserved eukaryotic TCTP (translationally controlled tumour protein) which is involved in a plethora of functions during growth and development and also acts as a biomarker for many cancers like lung, breast, and prostate cancer. The modelled TCTP structures of different organisms belonging to the eukaryotic group showed similar spatial arrangement of structural units except loops and similar patterns of root mean square deviation (RMSD), root mean square fluctuation, and radius of gyration (Rg) inspected through molecular dynamics simulations. Essential dynamics (ED) analyses revealed different domains that exhibited different motions for the assistance in its multifunctional properties. Construction of a free-energy landscape (FEL) based on Rg versus RMSD was employed to characterize the folding behaviours of structures and observe that all proteins had nearly similar conformation and topologies, indicating common thermodynamic/kinetic pathways. A physico-chemical interaction study demonstrated the helices and sheets were well stabilized with ample amounts of bonding compared to turns or loops and charged residues were more accessible to solvent molecules. Hence, the current study reveals the important structural features of TCTP that aid in diverse functions in a wide range of organisms, thus extending our knowledge of TCTP and also providing a venue for designing the potent inhibitors against it.

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All data generated or analyzed during this study are included in this article/supplementary material.

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Funding

Partial funding from DST-PURSE, DST-FIST, UGC Networking, and UPE II to S.S. is acknowledged. R.K. thanks the Indian Council of Medical Research for the research fellowship.

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  1. School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India

    Rakesh Kumar & Shweta Saran

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  1. Rakesh Kumar
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  2. Shweta Saran
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R.K. conceptualized, designed, and performed the experiments. R.K. and S.S. analyzed the data and wrote the manuscript. Both the authors reviewed and approved the final version of the manuscript.

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Correspondence to Shweta Saran.

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Kumar, R., Saran, S. Comparative modelling unravels the structural features of eukaryotic TCTP implicated in its multifunctional properties: an in silico approach. J Mol Model 27, 20 (2021). https://doi.org/10.1007/s00894-020-04630-y

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