[1P-35*] Dynamics of Close-Open State of CALB Obtained by Parallel Cascade Molecular Dynamics Simulation and The Markov State Model
Candida antarctica lipase B (CALB) is a versatile enzyme that is used in biofuel production and chemical synthesis. CALB active site is accessed through a lid region which is important in the catalysis mechanism of CALB. Molecular dynamics simulation (MD) is a class of computational methods that could unravel the motion of biomolecules at atomistic level which is difficult to probe by experimental methods. Among available MD methods, Parallel Cascade Molecular Dynamics Simulation (PaCS-MD) could explore biologically relevant rare events of biomolecules which are difficult to observe by conventional MD. We used both conventional MD and PaCS-MD to simulate CALB in solution. PaCS-MD successfully explored the close to open transition of the lid region while conventional MD simulations were trapped in the close and semi-open region. Free energy landscape constructed using the Markov State Model shows two distinct basins of energy minima which correspond to open and close/semi-open conformation of CALB. The close/semi-open conformation occupies more energetically favorable region of the free energy landscape, indicating that CALB is predominantly in close/semi-open conformation in water environment.