Lessons learned about steered molecular dynamics simulations and free energy calculations.

Area of Science:

• Computational chemistry and biophysics.
• Molecular dynamics simulations.
• Free energy calculations.

Background:

• Free energy profiles are crucial for understanding enzymatic activity, ligand migration, and conformational changes.
• Steered molecular dynamics (sMD) combined with the Jarzynski equality is a common method for calculating these profiles.
• The stiff-spring approximation and Gaussian work distributions are relevant concepts in sMD.

Purpose of the Study:

• To review the application of the Jarzynski equality to sMD simulations.
• To revisit the stiff-spring approximation and its implications for work distributions.
• To highlight the utility of the second-order cumulant expansion in sMD.

Main Methods:

• Application of the Jarzynski equality to steered molecular dynamics (sMD) simulations.
• Utilizing the second-order cumulant expansion for free energy calculations.
• Simulations of carbon monoxide (CO) in aqueous solution and a carbon nanotube.

Main Results:

• The second-order cumulant expansion aligns with the parametric maximum-likelihood estimator in this context.
• Simulations in both aqueous and nanoheterogeneous environments were performed.
• The study confirms the practical utility of the second-order cumulant expansion.

Conclusions:

• The second-order cumulant expansion enables faster pulling velocities in sMD simulations.
• This approach avoids introducing bias from non-equilibrium work distribution dispersion.
• It offers a practical and efficient method for free energy calculations in complex systems.