Okimoto Noriaki, Nakamura Takashi, Suenaga Atsushi, Futatsugi Noriyuki, Hirano Yoshinori, Yamaguchi Isamu, Ebisuzaki Toshikazu
Contribution from the Computational Astrophysics Laboratory, Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
J Am Chem Soc. 2004 Oct 13;126(40):13132-9. doi: 10.1021/ja048053u.
Two molecular dynamics (MD) simulations totaling 25 ns of simulation time of monomeric scytalone dehydratase (SD) were performed. The enzyme has a ligand-binding pocket containing a cone-shaped alpha+beta barrel, and the C-terminal region covers the binding pocket. Our simulations clarified the difference in protein dynamics and conformation between the liganded protein and the unliganded protein. The liganded protein held the ligand molecule tightly and the initial structure was maintained during the simulation. The unliganded protein, on the other hand, fluctuated dynamically and its structure changed largely from the initial structure. In the equilibrium state, the binding pocket was fully solvated by opening of the C-terminal region, and the protein dynamics was connected with hydration water molecules entry into and release from the binding pocket. In addition, the cooperative motions of the unliganded protein and the hydration water molecules produced the path through the protein interior for ligand binding.
进行了两个分子动力学（MD）模拟，单体紫草素脱水酶（SD）的模拟总时长为25纳秒。该酶有一个配体结合口袋，其中包含一个锥形α+β桶，C端区域覆盖结合口袋。我们的模拟阐明了结合配体的蛋白质和未结合配体的蛋白质在蛋白质动力学和构象上的差异。结合配体的蛋白质紧紧地固定着配体分子，并且在模拟过程中保持初始结构。另一方面，未结合配体的蛋白质动态波动，其结构与初始结构相比发生了很大变化。在平衡状态下，结合口袋通过C端区域的打开而被完全溶剂化，并且蛋白质动力学与结合口袋中水分子的进入和释放相关联。此外，未结合配体的蛋白质和水分子的协同运动产生了通过蛋白质内部的配体结合路径。
