Advances in simulation methods, continued optimizations of atomistic force fields, and increases in available computational power have coupled together over the past few decades to transform our understanding of biomolecular structure, dynamics, interactions and function [1]. Such methods can aid in the design of new drugs, monitor how RNA and protein molecules fold, and aid in the interpretation of experimental data. Development of advanced “ensemble-based” sampling methodologies in the AMBER suite of programs, such as multidimensional replica-exchange molecular dynamics methods, running on large CPU and GPU resources as pushed the capabilities further. We are now able to reproducibly converge (in independent runs) the conformational ensembles of RNA tetranuclEducation Outreach Trainingides [2-4] and even RNA tetraloops. This provides a means to assess and validate the force fields and to test improvements or alterations to the force fields in a systematic manner. Using large ensembles of independent simulations poses significant data management and analysis issues which we continue address with further developments in the CPPTRAJ program optimization and parallelization [5]. To make better use of the data we are also exploring means to automatically mine and display the data, and also better means to search and disseminate the data (iBIOMES) [6, 7]. All of these issues, developments and current barriers will be discussed in the context of large-scale use of XSEDE and Blue Waters computational resources.
