Extensible and Scalable Adaptive Sampling on Supercomputers.

The accurate sampling of protein dynamics is an ongoing challenge despite the utilization of high-performance computer (HPC) systems. Utilizing only "brute force" molecular dynamics (MD) simulations requires an unacceptably long time to solution. Adaptive sampling methods allow a more effective sampling of protein dynamics than standard MD simulations. Depending on the restarting strategy, the speed up can be more than 1 order of magnitude. One challenge limiting the utilization of adaptive sampling by domain experts is the relatively high complexity of efficiently running adaptive sampling on HPC systems. We discuss how the ExTASY framework can set up new adaptive sampling strategies and reliably execute resulting workflows at scale on HPC platforms. Here, the folding dynamics of four proteins are predicted with no a priori information.

Characterization of the three-dimensional free energy manifold for the uracil ribonucleoside from asynchronous replica exchange simulations.

Replica exchange molecular dynamics has emerged as a powerful tool for efficiently sampling free energy landscapes for conformational and chemical transitions. However, daunting challenges remain in efficiently getting such simulations to scale to the very large number of replicas required to address problems in state spaces beyond two dimensions. The development of enabling technology to carry out such simulations is in its infancy, and thus it remains an open question as to which applications demand extension into higher dimensions. In the present work, we explore this problem space by applying asynchronous Hamiltonian replica exchange molecular dynamics with a combined quantum mechanical/molecular mechanical potential to explore the conformational space for a simple ribonucleoside. This is done using a newly developed software framework capable of executing >3,000 replicas with only enough resources to run 2,000 simultaneously. This may not be possible with traditional synchronous replica exchange approaches. Our results demonstrate 1.) the necessity of high dimensional sampling simulations for biological systems, even as simple as a single ribonucleoside, and 2.) the utility of asynchronous exchange protocols in managing simultaneous resource requirements expected in high dimensional sampling simulations. It is expected that more complicated systems will only increase in computational demand and complexity, and thus the reported asynchronous approach may be increasingly beneficial in order to make such applications available to a broad range of computational scientists.