Figure 2.

Bias-based free energy estimates averaged over 32 runs of 8 ns for four different metadynamics choices designed to give different levels of resolution of the high-energy regions. Clockwise from top left: WTMetaD, TTMetaD, 15 kJ/mol transition-referenced MBMetaD, 42.5 kJ/mol minimum-referenced MBMetaD. All methods use parameters as defined in the text. Contours are placed every 5 kJ/mol. The estimates are all but identical in low-energy regions despite stark differences in the high-energy regions. WTMetaD is least controllable and gives the most resolution of high energy regions, TTMetaD is more controllable but would give more and more resolution of high energy regions given additional convergence time, and both forms of MBMetaD are fully controllable, converging without resolving the high energy regions.