ExTASY 0.1 Beta Testing 1 st April

Enhanced Sampling To efficiently and accurately identify particular alternative conformations of a molecule. – E.g., starting from an apo- conformation, identify alternative low energy conformations of a protein relevant to ligand binding (induced fit/conformational selection). To efficiently and accurately sample ALL conformational space for a molecule. – E.g. calculation of thermodynamic and kinetic parameters. Faster MD through hardware and software developments, e.g.: – multicore architectures + domain decomposition. – specialized hardware (ANTON, GRAPE,…) Faster MD through manipulation of the effective potential energy surface, e.g.: – metadynamics. – accelerated dynamics. Faster sampling through multiple simulation strategies, e.g.: – Replica exchange – Swarm/ensemble simulations + Markov chain models WHY HOW

The ExTASY Approach Use swarm/ensemble simulation strategies that map efficiently onto HPC services. Use smart collective coordinate strategies to focus sampling in interesting regions. Rely on machine learning methods rather than user expertise to select and refine (on the fly) the collective coordinates. Be compatible with standard MD codes out of the box (without software patches).

Iterative cycles that feature: – Many short MD simulations to sample regions of conformational space. – Data analysis steps that use collective coordinate methods to identify optimal start points for the next cycle of MD. Swarms/ensembles of MD simulations Analysis of trajectories Selection of new start points The ExTASY Workflow Two options implemented: – Simulations with GROMACS, or AMBER. – Data analysis using LSDMap (based on locally- scaled diffusion map analysis), or CoCo (based on PCA).

ExTASY Execution Model

Beta Testing Instructions For testing, we have provided access to ARCHER, using your accounts in project ‘e290’ We have 10 nodes reserved 2pm-5pm, to avoid queuing with all other jobs on the system To use our reservation set in your.rcfg file: QUEUE = ‘R ’ as well as other values described in the documentation

Beta Testing Instructions On the ExTASY website, there is a ‘User Guide’ – Instructions on how to use the tools, with examples – Start here if you have your own system, or want to set up everything from scratch! Also a ‘Tutorial’ – Detailed walk-though with all files provided – Start here if you just want to get something running!

Beta Testing Instructions We want your feedback: – Documentation: Do we tell you what you need to know. Too much? Too little? Anything missing? – Bugs: Any problems installing / using ExTASY – Features / suggestions: Does ExTASY provide a good abstraction that would allow you to express your own MD / Analysis workflow? What would you like to see added? to

Beta Testing Instructions Get started: We are here to help if needed! Just ask via Skype video or chat