Umbrella sampling and double decoupling data for methanol binding to Candida antarctica lipase B

Area of Science:

• Biochemistry
• Computational Chemistry
• Enzyme Kinetics

Background:

• Candida antarctica lipase B (CALB) is a widely used enzyme in biocatalysis.
• Understanding enzyme-ligand interactions, such as methanol binding to CALB, is crucial for optimizing enzymatic reactions.
• Accurate free-energy calculations are essential for predicting binding affinities and reaction mechanisms.

Purpose of the Study:

• To calculate the binding free-energy profile of methanol to CALB at infinite dilution and 6.1 M concentration.
• To validate molecular dynamics simulation results using alchemical double decoupling methods.
• To provide data for validating direct counting simulations and studying concentration-dependent binding effects.

Main Methods:

• Umbrella sampling molecular dynamics simulations with the OPLS all-atom force field.
• Alchemical double decoupling simulations for result validation.
• Calculation of binding free-energy profiles at different methanol concentrations.

Main Results:

• The binding free-energy profile of methanol to CALB was successfully computed at two distinct methanol concentrations.
• The simulation protocol was validated, demonstrating its reliability for related systems.
• The generated data serves as a benchmark for assessing alternative free energy calculation methods.

Conclusions:

• The study provides a robust computational protocol for determining enzyme-ligand binding free energies.
• The results highlight the importance of considering concentration effects in enzymatic binding studies.
• This work facilitates further research into enzyme kinetics and the development of novel computational approaches.