Generalized gradient-augmented harmonic Fourier beads method with multiple atomic and/or center-of-mass positional...

We describe a generalization of the gradient-augmented harmonic Fourier beads method for finding minimum free-energy transition path ensembles and similarly minimum potential energy paths to allow positional restraints on the centers of mass of selected atoms. The generalized gradient-augmented harmonic Fourier beads (ggaHFB) method further extends the scope of the HFB methodology to studying molecule transport across various mobile phases such as lipid membranes. Furthermore, the new implementation improves the applicability of the HFB method to studies of ligand binding, protein folding, and enzyme catalysis as well as modeling equilibrium pulling experiments. Like its predecessor, the ggaHFB method provides accurate energy profiles along the specified paths and in certain simple cases avoids the need for path optimization. The utility of the ggaHFB method is demonstrated with an application to the water permeation through a single-wall (5,5) carbon nanotube with a diameter of 6.78 A and length of 16.0 A. We provide a simple rationale as to why water enters the hydrophobic nanotube and why it does so in pulses and in wire assembly.