Twenty years of path sampling: origins and recent developments

Peter Bolhuis
Universiteit van Amsterdam
Department of Chemistry

In the two decades since its inception transition path sampling (TPS) has become an (almost) standard technique in the molecular dynamics toolbox. The great advantage of path sampling is that by focusing on the pathways undergoing the activated event, TPS avoids the problem of the choice of good collective variables to describe the reaction coordinate. This problem hampers many enhanced sampling methods based on molecular dynamics, as the omission of the pertinent collective variables can lead to dramatically wrong estimates of rate constants and even mechanisms. Over the last twenty years many variants of TPS have been developed. Strangely enough, only recently it has become possible to efficiently perform large-scale TPS simulations on complex systems, such as clathrate nucleation and protein dissociation.

Another strand of development is the transition interface sampling (TIS) methodology and the application to multiple states. I will give a brief overview of these developments and discuss case studies on DNA base pair rolling, and protein conformational changes. The resulting path ensembles also allow extraction of a low dimensional description of the reaction coordinates.

Furthermore, I will discuss the benefits of replica exchange versions of TPS and TIS and the computational reduction achieved by single replica multiple state TIS using a small model protein. All these advanced techniques are now made available through the OpenPathSampling platform.

Finally, I will come full circle and present a novel TPS approach based on nested sampling and apply it to the same small Lennard-Jones clusters that were used in the seminal path sampling papers 20 years ago.

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