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Article

Configurational Entropy of Folded Proteins and Its Importance for Intrinsically Disordered Proteins

1
Department of Chemistry, Beijing Normal University, Beijing 100875, China
2
Pitzer Center for Theoretical Chemistry, University of California, Berkeley, CA 94720, USA
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Department of Chemistry, University of California, Berkeley, CA 94720, USA
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Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA 94720, USA
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Molecular Medicine Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
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Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada
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Department of Bioengineering, University of California, Berkeley, CA 94720, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Istvan Simon and Csaba Magyar
Int. J. Mol. Sci. 2021, 22(7), 3420; https://doi.org/10.3390/ijms22073420
Received: 7 March 2021 / Revised: 24 March 2021 / Accepted: 25 March 2021 / Published: 26 March 2021
(This article belongs to the Special Issue Frontiers in Protein Structure Research)
Many pairwise additive force fields are in active use for intrinsically disordered proteins (IDPs) and regions (IDRs), some of which modify energetic terms to improve the description of IDPs/IDRs but are largely in disagreement with solution experiments for the disordered states. This work considers a new direction—the connection to configurational entropy—and how it might change the nature of our understanding of protein force field development to equally well encompass globular proteins, IDRs/IDPs, and disorder-to-order transitions. We have evaluated representative pairwise and many-body protein and water force fields against experimental data on representative IDPs and IDRs, a peptide that undergoes a disorder-to-order transition, for seven globular proteins ranging in size from 130 to 266 amino acids. We find that force fields with the largest statistical fluctuations consistent with the radius of gyration and universal Lindemann values for folded states simultaneously better describe IDPs and IDRs and disorder-to-order transitions. Hence, the crux of what a force field should exhibit to well describe IDRs/IDPs is not just the balance between protein and water energetics but the balance between energetic effects and configurational entropy of folded states of globular proteins. View Full-Text
Keywords: configurational entropy; force fields; intrinsically disordered proteins configurational entropy; force fields; intrinsically disordered proteins
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MDPI and ACS Style

Liu, M.; Das, A.K.; Lincoff, J.; Sasmal, S.; Cheng, S.Y.; Vernon, R.M.; Forman-Kay, J.D.; Head-Gordon, T. Configurational Entropy of Folded Proteins and Its Importance for Intrinsically Disordered Proteins. Int. J. Mol. Sci. 2021, 22, 3420. https://doi.org/10.3390/ijms22073420

AMA Style

Liu M, Das AK, Lincoff J, Sasmal S, Cheng SY, Vernon RM, Forman-Kay JD, Head-Gordon T. Configurational Entropy of Folded Proteins and Its Importance for Intrinsically Disordered Proteins. International Journal of Molecular Sciences. 2021; 22(7):3420. https://doi.org/10.3390/ijms22073420

Chicago/Turabian Style

Liu, Meili, Akshaya K. Das, James Lincoff, Sukanya Sasmal, Sara Y. Cheng, Robert M. Vernon, Julie D. Forman-Kay, and Teresa Head-Gordon. 2021. "Configurational Entropy of Folded Proteins and Its Importance for Intrinsically Disordered Proteins" International Journal of Molecular Sciences 22, no. 7: 3420. https://doi.org/10.3390/ijms22073420

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