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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Feb 15

PMID 35163513

Authors

Shu-Shun Hsueh

S-S Steven Wang

Shu-Han Chen

Chia-Lin Wang

W Josephine Wu

Ta-Hsien Lin

Affiliations

Soon will be listed here.

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.

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