Insights to Human γD-Crystallin Unfolding by NMR Spectroscopy and Molecular Dynamics Simulations

Hsueh, Shu-Shun; Wang, S.-S. (Steven); Chen, Shu-Han; Wang, Chia-Lin; Wu, W. (Josephine); Lin, Ta-Hsien

doi:10.3390/ijms23031591

Open AccessArticle

Insights to Human γD-Crystallin Unfolding by NMR Spectroscopy and Molecular Dynamics Simulations

by

Shu-Shun Hsueh

^1,†,

S.-S. (Steven) Wang

^1,†,

Shu-Han Chen

¹,

Chia-Lin Wang

²,

W. (Josephine) Wu

^3,* and

Ta-Hsien Lin

^2,4,*

¹

Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan

²

Laboratory of Nuclear Magnetic Resonance, Medical Research Department, Taipei Veterans General Hospital, Taipei 11217, Taiwan

³

Department of Optometry, Yuanpei University of Medical Technology, Hsinchu City 30015, Taiwan

⁴

Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2022, 23(3), 1591; https://doi.org/10.3390/ijms23031591

Submission received: 26 November 2021 / Revised: 13 January 2022 / Accepted: 19 January 2022 / Published: 29 January 2022

(This article belongs to the Collection Feature Papers in Molecular Biophysics)

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Abstract

Human γD-crystallin (HGDC) is an abundant lens protein residing in the nucleus of the human lens. Aggregation of this and other structural proteins within the lens leads to the development of cataract. Much has been explored on the stability and aggregation of HGDC and where detailed investigation at the atomic resolution was needed, the X-ray structure was used as an initial starting conformer for molecular modeling. In this study, we implemented NMR-solution HGDC structures as starting conformers for molecular dynamics simulations to provide the missing pieces of the puzzle on the very early stages of HGDC unfolding leading up to the domain swap theories proposed by past studies. The high-resolution details of the conformational dynamics also revealed additional insights to possible early intervention for cataractogenesis.

Keywords: human γD-crystallin; stability; unfolding; aggregation; cataract; NMR spectroscopy; molecular dynamics simulations

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MDPI and ACS Style

Hsueh, S.-S.; Wang, S.-S.; Chen, S.-H.; Wang, C.-L.; Wu, W.; Lin, T.-H. Insights to Human γD-Crystallin Unfolding by NMR Spectroscopy and Molecular Dynamics Simulations. Int. J. Mol. Sci. 2022, 23, 1591. https://doi.org/10.3390/ijms23031591

AMA Style

Hsueh S-S, Wang S-S, Chen S-H, Wang C-L, Wu W, Lin T-H. Insights to Human γD-Crystallin Unfolding by NMR Spectroscopy and Molecular Dynamics Simulations. International Journal of Molecular Sciences. 2022; 23(3):1591. https://doi.org/10.3390/ijms23031591

Chicago/Turabian Style

Hsueh, Shu-Shun, S.-S. (Steven) Wang, Shu-Han Chen, Chia-Lin Wang, W. (Josephine) Wu, and Ta-Hsien Lin. 2022. "Insights to Human γD-Crystallin Unfolding by NMR Spectroscopy and Molecular Dynamics Simulations" International Journal of Molecular Sciences 23, no. 3: 1591. https://doi.org/10.3390/ijms23031591

APA Style

Hsueh, S.-S., Wang, S.-S., Chen, S.-H., Wang, C.-L., Wu, W., & Lin, T.-H. (2022). Insights to Human γD-Crystallin Unfolding by NMR Spectroscopy and Molecular Dynamics Simulations. International Journal of Molecular Sciences, 23(3), 1591. https://doi.org/10.3390/ijms23031591

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Insights to Human γD-Crystallin Unfolding by NMR Spectroscopy and Molecular Dynamics Simulations

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