Wijaya Tegar N, Kitao Akio
School of Life Science and Technology, Tokyo Institute of Technology. 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan.
Department of Chemistry, Universitas Pertamina, Jl. Teuku Nyak Arief, Simprug, Jakarta 12220, Indonesia.
J Phys Chem B. 2023 Aug 31;127(34):7431-7441. doi: 10.1021/acs.jpcb.3c02041. Epub 2023 Aug 10.
The conformational dynamics of lipase B (CALB) was investigated by molecular dynamics (MD) simulation, parallel cascade selection MD (PaCS-MD), and the Markov state model (MSM) and mainly focused on the lid-opening motion closely related to substrate binding. All-atom MD simulation of CALB was conducted in water and on the interface of water and tricaprylin. CALB initially situated in water and separated by layers of water from the interface is spontaneously adsorbed onto the tricaprylin surface during MD simulation. The opening and closing motions of the lid are simulated by PaCS-MD, and subsequent MSM analysis provided the free-energy landscape and time scale of the conformational transitions among the closed, semiopen, and open states. The closed state is the most stable in the water system, but the stable conformation in the interface system shifts to the semiopen state. These effects could explain the energetics and kinetics origin of the previously reported interfacial activation of CALB. These findings could help expand the application of CALB toward a wide variety of substrates.
通过分子动力学（MD）模拟、平行级联选择MD（PaCS-MD）和马尔可夫状态模型（MSM）研究了脂肪酶B（CALB）的构象动力学，主要关注与底物结合密切相关的盖子打开运动。CALB的全原子MD模拟在水中以及水和三辛酸甘油酯的界面上进行。在MD模拟过程中，最初位于水中且与界面被水层隔开的CALB会自发吸附到三辛酸甘油酯表面。通过PaCS-MD模拟盖子的打开和关闭运动，随后的MSM分析提供了封闭、半开放和开放状态之间构象转变的自由能景观和时间尺度。封闭状态在水体系中最稳定，但在界面体系中稳定构象转变为半开放状态。这些效应可以解释先前报道的CALB界面激活的能量学和动力学起源。这些发现有助于扩大CALB对多种底物的应用。
