Adaptive partitioning by local density-peaks: An efficient density-based clustering algorithm for analyzing molecular dynamics trajectories.

We present an efficient density-based adaptive-resolution clustering method APLoD for analyzing large-scale molecular dynamics (MD) trajectories. APLoD performs the k-nearest-neighbors search to estimate the density of MD conformations in a local fashion, which can group MD conformations in the same high-density region into a cluster. APLoD greatly improves the popular density peaks algorithm by reducing the running time and the memory usage by 2-3 orders of magnitude for systems ranging from alanine dipeptide to a 370-residue Maltose-binding protein. In addition, we demonstrate that APLoD can produce clusters with various sizes that are adaptive to the underlying density (i.e., larger clusters at low-density regions, while smaller clusters at high-density regions), which is a clear advantage over other popular clustering algorithms including k-centers and k-medoids. We anticipate that APLoD can be widely applied to split ultra-large MD datasets containing millions of conformations for subsequent construction of Markov State Models. © 2016 Wiley Periodicals, Inc.