Implementation of the forward-reverse method for calculating the potential of mean force using a dynamic restraining...

Area of Science:

• Computational chemistry
• Biophysics
• Molecular dynamics simulations

Background:

• Calculating potential of mean force (PMF) is crucial for understanding molecular interactions.
• Steered molecular dynamics (SMD) simulations often face challenges in sampling and convergence.
• Existing methods may struggle with accurate separation of work distributions.

Purpose of the Study:

• To present a novel sampling and analysis scheme, the bin-passing method, for calculating PMF in SMD simulations.
• To enhance sampling efficiency and accelerate convergence to accurate PMF.
• To provide a publicly available software tool for post-simulation analysis.

Main Methods:

• The bin-passing method, based on the forward-reverse (FR) method and thermodynamic principles.
• Application to three diverse systems: NaCl dissociation in water, water permeation through a DPPC bilayer, and peptide-membrane interactions.
• Utilizing a purpose-built, publicly available software analyzer.

Main Results:

• Achieved excellent agreement with static methods for NaCl dissociation PMF.
• Obtained a highly symmetric PMF for water passage through a DPPC bilayer, yielding improved permeability values.
• Characterized HHC-36 peptide adsorption to membranes, consistent with experimental findings on its antimicrobial properties.

Conclusions:

• The bin-passing method offers enhanced sampling and faster convergence for PMF calculations in SMD.
• The method demonstrates high accuracy across various systems, from small ions to complex peptide-membrane interactions.
• The developed software facilitates the application and analysis of this efficient PMF calculation technique.