Gaussian Accelerated Molecular Dynamics: Unconstrained Enhanced Sampling and Free Energy Calculation

Area of Science:

• Computational chemistry
• Biophysics
• Molecular dynamics

Background:

• Enhanced sampling methods are crucial for studying complex biomolecular systems.
• Free energy calculations provide quantitative insights into molecular interactions and processes.
• Traditional methods often require predefined reaction coordinates, limiting exploration.

Purpose of the Study:

• To introduce a novel Gaussian accelerated molecular dynamics (GaMD) approach.
• To enable simultaneous enhanced sampling and free energy calculations for biomolecules.
• To demonstrate GaMD's utility on diverse biomolecular systems.

Main Methods:

• Development of a boost potential following a Gaussian distribution.
• Accurate reweighting of GaMD simulations using second-order cumulant expansion.
• Application to alanine dipeptide, chignolin folding, and T4-lysozyme ligand binding.

Main Results:

• GaMD achieved unconstrained enhanced sampling without predefined reaction coordinates.
• Accurate free energy profiles were obtained through reweighted GaMD simulations.
• Distinct low-energy states and molecular pathways were identified.

Conclusions:

• GaMD provides an efficient and accurate method for biomolecular enhanced sampling and free energy calculations.
• The approach facilitates the quantitative characterization of protein folding and ligand-binding pathways.
• GaMD offers a powerful tool for exploring complex biomolecular dynamics.