Abstract
The conformational dynamics of Candida antarctica 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.