Lid Closure Mechanism of <i>Yarrowia lipolytica</i> Lipase in Methanol Investigated by Molecular Dynamics Simulation

In nonaqueous organic solvents, lipases can catalyze esterification reactions, which increase their application value. <i>Yarrowia lipolytica</i> Lipase (Lip2) possesses potential values in medicine and industrial production. In order to investigate its lid closure mechanism in methanol we performed molecular dynamics (MD) simulations of the open conformation of Lip2 in methanol and hexane, respectively. Simulation results indicated that Lip2 undergoes a greater conformational change in methanol. Principle component analysis showed Lip2 has “double-domain” and “torsion” motion modes in hexane and methanol. By analyzing B-factor and dynamical cross-correlation, region Ser274-Asn288, region Thr106-His126, and region Asp61-Asp67 were found to interact with the lid region (Thr88-Leu105). Furthermore, local restricted MD simulations showed that closure mechanism of Lip2 is “double-lid movement” which is also observed in <i>Pseudomonas aeruginosa</i> Lipase (PAL), and we detected two interaction propagation pathways in Lip2 driven by the interaction between Ser274-Asn288 and methanol