  Modern potential energy surfaces have shifted attention to molecular
simulations of chemical reactions. While various methods can estimate rate
constants for conformational transitions in molecular dynamics simulations,
their applicability to studying chemical reactions remains uncertain due to the
high and sharp energy barriers and complex reaction coordinates involved. This
study focuses on the thermal cis-trans isomerization in retinal, employing
molecular simulations and comparing rate constant estimates based on
one-dimensional rate theories with those based on sampling transitions and
grid-based models for low-dimensional collective variable spaces. Even though
each individual method to estimate the rate passes its quality tests, the rate
constant estimates exhibit disparities of up to four orders of magnitude. Rate
constant estimates based on one-dimensional reaction coordinates prove
challenging to converge, even if the reaction coordinate is optimized. However,
consistent estimates of the rate constant are achieved by sampling transitions
and by multi-dimensional grid-based models.

Chemical Physics