Overcoming Sampling Issues and Improving Computational Efficiency in Collective-Variable-Based Enhanced-Sampling Simulations: A Tutorial

This tutorial is designed to help users overcome sampling
challenges
and improve computational efficiency in collective-variable (CV)-based
enhanced-sampling, or importance-sampling, simulations. Toward this
end, we introduce well-tempered metadynamics-extended adaptive biasing
force (WTM-eABF) and its integration with Gaussian accelerated molecular
dynamics (GaMD). Additionally, use will be made of a method for identifying
the least-free-energy pathway (LFEP) and multiple concurrent pathways
on high-dimensional free-energy surfaces. We illustrate these sampling
techniques with the conformational equilibria of trialanine and chignolin
in aqueous solution as test cases. This tutorial assumes that the
user has prior experience with molecular dynamics (MD) simulations,
in general, with the popular program NAMD, and to some extent with
Colvars, the module for CV-based calculations. This tutorial can,
however, in large measure be used in conjunction with alternate MD
engines that support the Colvars module such as GROMACS, LAMMPS, and
Tinker-HP.