Abstract
Molecular dynamics (MD) simulations are ideally suited to describe conformational ensembles of biomolecules such as proteins and nucleic acids. Microsecond-long simulations are now routine, facilitated by the emergence of graphical processing units. Clustering, which groups objects based on structural similarity, is typically used to process ensembles, leading to different states, their populations, and the identification of representative structures. A popular pipeline combines hierarchical clustering for clustering and selecting the cluster centroid as representative of the cluster. Here, we propose to improve on this approach, by developing a module-Protein Retrieval via Integrative Molecular Ensembles (PRIME), that consists of tools to improve the prediction of the representative in the most populated cluster using extended continuous similarity. PRIME is integrated with our Molecular Dynamics Analysis with N-ary Clustering Ensembles (MDANCE) package and can be used as a postprocessing tool for arbitrary clustering algorithms, compatible with several MD suites. PRIME predictions produced structures that when aligned to the experimental structure were better superposed (lower RMSD). A further benefit of PRIME is its linear scaling─rather than the traditional O(N(2)) traditionally associated with comparisons of elements in a set.