Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan.
Laboratory of Nuclear Magnetic Resonance, Medical Research Department, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
Int J Mol Sci. 2022 Jan 29;23(3):1591. doi: 10.3390/ijms23031591.
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.
人γD-晶体蛋白（HGDC）是一种丰富的晶状体蛋白，位于人晶状体的核内。这种和其他结构蛋白在晶状体中的聚集导致白内障的发生。人们对 HGDC 的稳定性和聚集性进行了大量的研究，在需要原子分辨率的详细研究中，X 射线结构被用作分子建模的初始起始构象。在这项研究中，我们采用 NMR 溶液 HGDC 结构作为分子动力学模拟的起始构象，以提供在导致过去研究提出的结构域交换理论的 HGDC 展开的早期阶段缺失的部分。构象动力学的高分辨率细节还揭示了白内障发生的可能早期干预的更多见解。
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