Exciting news! Our international team, consisting of members from both the CCU and the UW teams and led by MYT, has had our work accepted for publication in The Journal of Physical Chemistry B (J. Phys. Chem. B, https://pubs.acs.org/doi/abs/10.1021/acs.jpcb.3c07938)! This marks my first research article since joining National Chung Cheng University (CCU).
Research often requires understanding biomolecular interactions and their structural characteristics. The Protein Data Bank (PDB) offers many such structures obtained through various methods. However, do these structures fully represent reality? For instance, structures from X-ray crystallography may differ from other experiments due to crystallization conditions.
Our recent study focused on cofilin, an actin-binding protein regulating the dynamics of the actomyosin network. It acts as a monomer to sever actin fibers or as an oligomer to aid in protein assembly. We found that cofilin dimers can take various configurations depending on how their cysteine residues form bonds under cellular oxidative stress. Molecular simulations showed stable configurations, including a symmetrical dimer that may precede active oligomer formation.
I'd like to extend my sincere gratitude to my collaborator, Prof. Margaret Cheung, a Scientist at Pacific Northwest National Laboratory and Affiliate Professor at the University of Washington, for her invaluable support throughout this endeavor. I also want to acknowledge the outstanding contributions of our two talented students, Chengxuan Li from UW and Tingyi Wei from CCU. Their dedication and hard work have truly made this collaboration a success! 🎉
恭喜由MYT領導的國際團隊（中正大學團隊和UW團隊！這項工作已經被美國化學學會《物理化學期刊B》（J. Phys. Chem. B, https://pubs.acs.org/doi/abs/10.1021/acs.jpcb.3c07938）接受發表！這是MYT加入國立中正大學後的第一篇研究論文。
研究生物分子相互作用的課題通常需要了解其結構特性，尤其是在使用電腦建立分子模型並模擬其運動軌跡時。這些模型需要參考實驗結構作為基礎，而蛋白質數據庫（PDB）中包含了許多通過X射線、核磁共振（NMR）和冷凍電子顯微鏡（cryoEM）等方法獲得的生物分子結構。但是，這些結構資訊是否完全反映了真實情況呢？例如，通過X射線結晶得到的分子結構可能在實驗條件上與其他生物活性實驗存在差異。
我們的研究團隊最近發現了這個問題的答案是否定的，並提出解釋。PDB上公開的生物分子結構資訊可能未必完全反映真實情況。我們的研究聚焦於一種名為絲切蛋白的肌動蛋白結合蛋白，它在細胞中調節肌動蛋白網絡的斷裂和組裝，其功能取決於其單體或寡聚體狀態。單體時，絲切蛋白能夠切斷肌動蛋白纖維並促進單體再循環，而在寡聚體形成時，則參與了肌動蛋白的核化和組裝，進而影響細胞骨架的組織和重塑。
我們的研究發現，絲切蛋白形成二聚體時，可透過不同的蛋白質結合介面形成多種組態，這取決於其半胱氨酸在細胞氧化壓力下與另一個絲切蛋白的半胱氨酸形成的雙硫鍵對。我們利用分子動力學模擬研究了這些二聚體的構型和穩定性，並發現了能量上穩定的結構，其中一個具有對稱性構造的二聚體可能是形成生物活性寡聚體（例如四聚體）的先驅物。
我要感謝我的合作者Margaret Cheung教授（太平洋西北國家實驗室的科學家、華盛頓大學的兼任教授），她給予了我很大的支持。這項工作由兩位優秀的學生Chengxuan Li（華盛頓大學物理系）和魏亭宜（中正大學化生系）合力完成。這是非常棒的研究工作！
