Rare Event Kinetics from Adaptive Bias Enhanced Sampling

Abstract

We introduce a novel enhanced sampling approach named on-the-fly probability enhanced sampling (OPES) flooding for calculating the kinetics of rare events from atomistic molecular dynamics simulation. This method is derived from the OPES approach [Invernizzi and Parrinello,

Stochastic Resetting for Enhanced Sampling

“…A similar trade-off was also observed by Ray et al for the OPES flooding enhanced sampling method. 53 For this benchmark, we obtained an error of ∼10% in the prediction of the unbiased mean FPT for a speedup of ∼1.7, an error of ∼50% for a speedup of ∼2.8, an error of ∼100% for a speedup of ∼3.9, and an error of ∼500% for a speedup of ∼8.0. Also, in the case of inference, the strength of SR is that it does not require identifying efficient collective variables.…”

“…The final model system is presented in the bottom row of Figure . It is a modified version of the Wolfe–Quapp potential, often used for benchmarking enhanced sampling methods. ,, This potential has two metastable basins, one at y < 0 and the other at y > 0. The former is divided into two substates that have similar width and depth.…”

“…Despite many recent advancements, ,,,, evaluating the rates of long time scale processes from enhanced simulations is still very challenging, and they can deviate by orders of magnitude from experiments . To increase the accuracy, methods such as infrequent metadynamics or OPES flooding use much weaker biasing, ,,, and the resulting speedups are significantly lower than standard metadynamics. Here, we employ SR for this purpose, showing that it is not limited to expediting transitions but can also be used for inferring kinetics.…”

“…This results in a trade-off between precision and speedup. A similar trade-off was also observed by Ray et al for the OPES flooding enhanced sampling method . For this benchmark, we obtained an error of ∼10% in the prediction of the unbiased mean FPT for a speedup of ∼1.7, an error of ∼50% for a speedup of ∼2.8, an error of ∼100% for a speedup of ∼3.9, and an error of ∼500% for a speedup of ∼8.0.…”

“… 56 Next, we tackle another major goal of enhanced sampling: the inference of the unbiased kinetics from biased simulations. Despite many recent advancements, 3 , 4 , 53 , 57 , 58 evaluating the rates of long time scale processes from enhanced simulations is still very challenging, and they can deviate by orders of magnitude from experiments. 59 To increase the accuracy, methods such as infrequent metadynamics or OPES flooding use much weaker biasing, 3 , 4 , 53 , 57 and the resulting speedups are significantly lower than standard metadynamics.…”