  We present a method to explore the free energy landscapes of chemical
reactions with post-transition-state bifurcations using an enhanced sampling
method based on well-tempered metadynamics. Obviating the need for
computationally expensive DFT-level ab initio molecular dynamics simulations,
we obtain accurate energetics by utilizing a free energy perturbation scheme
and deep learning estimator for the single-point energies of substrate
configurations. Using a pair of easily interpretable collective variables, we
present a quantitative free energy surface that is compatible with harmonic
transition state theory calculations and in which the bifurcations are clearly
visible. We demonstrate our approach with the example of the SpnF-catalyzed
Diels-Alder reaction, a cycloaddition reaction in which post-transition-state
bifurcation leads to the [4+2] as well as the [6+4] cycloadduct. We obtain the
free energy landscapes for different stereochemical reaction pathways and
characterize the mechanistic continuum between relevant reaction channels
without explicitly searching for the pertinent transition state structures.
