Low-Frequency Harmonic Perturbations Drive Protein Conformational Changes

Autor: Domenico Scaramozzino, Gianfranco Piana, Giuseppe Lacidogna, Alberto Carpinteri
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 19, p 10501 (2021)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms221910501
Popis: Protein dynamics has been investigated since almost half a century, as it is believed to constitute the fundamental connection between structure and function. Elastic network models (ENMs) have been widely used to predict protein dynamics, flexibility and the biological mechanism, from which remarkable results have been found regarding the prediction of protein conformational changes. Starting from the knowledge of the reference structure only, these conformational changes have been usually predicted either by looking at the individual mode shapes of vibrations (i.e., by considering the free vibrations of the ENM) or by applying static perturbations to the protein network (i.e., by considering a linear response theory). In this paper, we put together the two previous approaches and evaluate the complete protein response under the application of dynamic perturbations. Harmonic forces with random directions are applied to the protein ENM, which are meant to simulate the single frequency-dependent components of the collisions of the surrounding particles, and the protein response is computed by solving the dynamic equations in the underdamped regime, where mass, viscous damping and elastic stiffness contributions are explicitly taken into account. The obtained motion is investigated both in the coordinate space and in the sub-space of principal components (PCs). The results show that the application of perturbations in the low-frequency range is able to drive the protein conformational change, leading to remarkably high values of direction similarity. Eventually, this suggests that protein conformational change might be triggered by external collisions and favored by the inherent low-frequency dynamics of the protein structure.
Databáze: Directory of Open Access Journals
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