Here, to mimic what would happen in a binding site like that in T4 lysozyme where torsional rotation is blocked by the surrounding environ-ment, leading to very high barriers to rotamer swaps, we increase the periodic torsion force constant such that it creates a torsional barrier that is roughly equivalent to 10kcal/mol (16.9 k B T ). Compared to our unmodified valine-alanine system, there is a reduction in the total number of transitions between rotamer states and the transition frequently observed in MD decreases markedly (Figure ). When comparing transitions per nanosecond and transitions per force evaluation, BLUES exhibits a more favorable transition rate by both metrics when compared with MD (1.4±0.1 transitions/ns and 1.6±0.1 transitions/1e6 FEs for BLUES versus 0.50±0.04 transitions/ns and 1.1±0.1 transitions/1e6 FEs for MD). Thus, roughly as expected, BLUES becomes a better option for enhanced sidechain sampling as barriers to rotation grow larger.