CHARMM-GUI Enhanced Sampler for various collective variables and enhanced sampling methods

Area of Science:

• Computational Chemistry
• Molecular Dynamics Simulations
• Biophysics

Background:

• Conventional unbiased molecular dynamics (MD) simulations struggle with convergence for systems exhibiting rugged potential energy surfaces.
• Enhanced sampling methodologies offer solutions by modifying Hamiltonians to overcome these limitations.

Purpose of the Study:

• To introduce CHARMM-GUI Enhanced Sampler, a web-based tool for preparing enhanced sampling simulation inputs.
• To facilitate the use of user-selected collective variables (CVs) for various enhanced sampling techniques.

Main Methods:

• The tool supports nine enhanced sampling methods: accelerated MD, Gaussian accelerated MD, conformational flooding, metadynamics, adaptive biasing force, steered MD, temperature replica exchange MD, replica exchange solute tempering 2, and replica exchange umbrella sampling.
• It is compatible with major MD packages: AMBER, CHARMM, GENESIS, GROMACS, NAMD, and OpenMM.
• Users define nine common CVs (e.g., distance, angle, dihedral, RMSD, radius of gyration, coordination numbers) through an intuitive web interface.

Main Results:

• CHARMM-GUI Enhanced Sampler streamlines the setup of complex enhanced sampling simulations.
• The tool has been tested on biological systems, demonstrating the efficiency of enhanced sampling over conventional MD.
• Optimized system-dependent parameters are provided to ensure meaningful simulation outcomes.

Conclusions:

• CHARMM-GUI Enhanced Sampler significantly lowers the barrier for researchers to implement advanced enhanced sampling techniques.
• This tool empowers scientists to gain deeper insights into complex molecular systems that are intractable with standard MD simulations.