光觸發HP-36蛋白折疊之理論計算研究

Theoretical Investigation of the Photo-Initiated Folding of HP-36

林楷倫(Kai-Lun Lin) ； 李豐穎(Feng-Yin Li)

《化學》 65卷1期 (2007/03) Pp. 45-53

https://doi.org/10.6623/chem.2007006

摘要

本文利用理論計算模擬方法檢驗以光裂解(photolabile)有機分子連結之鍊鎖(caged)蛋白質的光觸發折疊反應，以證驗此種方法中有機連結處理是否仍具類似原有折疊動力行為。以36個胺基酸的雞絨毛蛋白(villin)為例，進行分子動力學模擬以光裂解的連結處理過變質(mutant)蛋白質，研究鍊鎖和開鎖(uncaged)結構變化，同時比較其與原生(wild-type)蛋白質折疊動力行為之差異。由其自由能景觀(free energy landscape)和計算旋光(Circular Dichroism, CD) 光譜之描述折疊的特性和結構，與已發表的實驗結果比較，我們發現由分子動力學模擬出的折疊結構與原生蛋白質的實驗所得結構相似。變質與原生的蛋白質的自由能景觀具有相似的拓樸結構，意味著兩者擁有類似的熱力學與動力學表現，然而兩者之自由能景觀略有不同，表示折疊動力行為尚有微小的差異，但不影響此種實驗方法對研究折疊動力行為之正當性。

關鍵字

光觸發折疊反應 ； 分子動力學模擬 ； 自由能景觀 ； 旋光光譜

並列摘要

A computational model was developed to examine the phototriggered folding of a caged protein, a protein modified with an organic photolabile cross-linker. Molecular dynamics simulations of the modified 36-residue fragment of subdomain B of chicken villin head piece with a photolabile linker were performed, starting from both the caged and the uncaged structures. Construction of a free-energy landscape, based on principal components as well as on radius of gyration vs. root-mean-square deviation, and circular dichroism calculations were employed to characterize folding behavior and structures. The folded structures observed in the molecular dynamics trajectories were found to be similar to that of the wild-type protein, in agreement with the published experimental results. The free-energy landscapes of the modified and wild-type proteins have similar topology, suggesting common thermodynamic/kinetic behavior. The existence of small differences in the free-energy surface of the modified protein from that of the native protein, however, indicates subtle differences in the folding behavior.

並列關鍵字

Phototriggered folding ； Molecular dynamics simulation ； Free energy landscape ； Circular Dichroism