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

Abstract

Enhanced sampling methodologies modifying underlying Hamiltonians can be used for the systems with a rugged potential energy surface that makes it hard to observe convergence using conventional unbiased molecular dynamics (MD) simulations. We present CHARMM-GUI Enhanced Sampler, a web-based tool to prepare various enhanced sampling simulations inputs with user-selected collective variables (CVs). Enhanced Sampler provides inputs for the following nine 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 for the method-implemented MD packages including AMBER, CHARMM, GENESIS, GROMACS, NAMD, and OpenMM. Users only need to select a group of atoms via intuitive web-implementation in order to define commonly used nine CVs of interest: center of mass based distance, angle, dihedral, root-mean-square-distance, radius of gyration, distance projected on axis, two types of angles projected on axis, and coordination numbers. The enhanced sampling methods are tested with several biological systems to illustrate their efficiency over conventional MD. Enhanced Sampler with carefully optimized system-dependent parameters will help users to get meaningful results from their enhanced sampling simulations.