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Rethinking the protein folding problem from a new perspective

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Abstract

One of the main concerns of Anfinsen was to reveal the connection between the amino-acid sequence and their biologically active conformation. This search gave rise to two crucial questions in structural biology, namely, why the proteins fold and how a sequence encodes its folding. As to the why, he proposes a plausible answer, namely, the thermodynamic hypothesis. As to the how, this remains an unsolved challenge. Consequently, the protein folding problem is examined here from a new perspective, namely, as an ‘analytic whole’. Conceiving the protein folding in this way enabled us to (i) examine in detail why the force-field-based approaches have failed, among other purposes, in their ability to predict the three-dimensional structure of a protein accurately; (ii) propose how to redefine them to prevent these shortcomings, and (iii) conjecture on the origin of the state-of-the-art numerical-methods success to predict the tridimensional structure of proteins accurately.

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Acknowledgements

The author acknowledges support from the IMASL-CONICET-UNSL and ANPCyT (PICT-02212), Argentina.

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  1. IMASL-CONICET, Universidad Nacional de San Luis, Ejército de Los Andes 950, 5700, San Luis, Argentina

    Jorge A. Vila

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  1. Jorge A. Vila
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Correspondence to Jorge A. Vila.

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Vila, J.A. Rethinking the protein folding problem from a new perspective. Eur Biophys J 52, 189–193 (2023). https://doi.org/10.1007/s00249-023-01657-w

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