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The rules for resampling trajectories without bias are extremely flexible and numerous possibilities are implemented within the WESTPA software. D35 and D39 are the barstar residues that become the most buried upon binding barnase.īinning: 72 bins with coarsely spaced bins every 1 Å from 10 to 60 Å and more finely spaced bins every 0.5 Å from 0 to 10 Å along the RMSD coordinate two bins along the distance coordinate separated by a bin boundary at 5 Å fixed total number of trajectories (1600)ġ600 CPU cores on a supercomputer (e.g. NTL9 protein in generalized Born (GB) implicit solvent with low and high solvent viscosity (collision frequency of 5 ps −1 and 80 ps −1 respectively): 627 atomsġD progress coordinate: C α RMSD from the folded structure.īinning: 53 bins, that are finely spaced for near-folded structures (35 bins for 1.0 Å 100,000 atomsĢD progress coordinate: (i) heavy-atom RMSD of barstar residues D35 and D39 after alignment on barnase, and (ii) minimum protein-protein separation distance. The rules typically generate trajectory replicates-which will diverge upon additional simulation using a stochastic thermostat or dynamics-in under-sampled regions while pruning trajectories that occur in over-sampled regions. The trajectory weights, which are fundamental to WE, result from the statistical resampling procedures which either prune or replicate trajectories according to rules implemented in WESTPA. These rare regions might be (free) energetic barriers or merely distant regions of configuration space. Īs sketched in Figure 1, the essence of WE is to use a statistically unbiased, weighted sample of MD trajectories in such a way that a higher density of trajectories is deployed in regions of configuration space where sampling would otherwise be rare in standard MD.
#Testout lab 6.4.6 software
The WESTPA software can be considered a direct descendent of the Huber and Kim algorithm, although the idea to use trajectory “splitting” and reweighting had been devised decades earlier for research at Los Alamos. The overall WE strategy can be embodied in a wide variety of specific algorithms. Typical examples are the calculation of pathways and rate constants for conformational and binding processes. The WE strategy organizes an array of MD trajectories strategically in configuration space to target quantities of interest which would not be calculable via standard MD. Īfter completing the Basic Tutorial involving the simulation of Na +/Cl − association, the user should be able to:
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This set of tutorials is restricted to applications in molecular dynamics (MD) simulations, but WE and WESTPA are applicable to arbitrary stochastic simulations. Learning objectives and expected outcomes are outlined for each tutorial.
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These tutorials can also be found online in the WESTPA GitHub repository ( ). Here we present a suite of five tutorials for the WESTPA software in order of difficulty from basic to advanced, including a tutorial involving the suite of analysis tools.
#Testout lab 6.4.6 free
This efficiency (relative to standard “brute force” simulations) has been demonstrated to increase exponentially with the effective free energy barrier of the rare event. The WESTPA software package has enabled efficient atomistic simulations of host-guest associations, protein binding processes, and protein folding. The WESTPA software also includes plugins for using a WE-based string method and a WE strategy utilizing hierarchical Voronoi bins (WExplore).
#Testout lab 6.4.6 full
Gromacs, Amber, OpenMM ) (ii) an optimized, parallel implementation of the WE strategy that exhibits perfect scaling out to >4000 CPU cores (iii) an effective suite of tools for analysis of the millions of files created by each simulation (iv) full extensibility for enhancements to simulation protocols and analysis tools and (v) portability of the software on any Unix-like computing resource, including typical computing clusters and supercomputers. Key features of WESTPA, written in Python, include (i) a general interface that enables interoperability with any dynamics engine (e.g. WESTPA (The Weighted Ensemble Simulation Toolkit with Parallelization and Analysis ) is an open-source, highly scalable software framework for carrying out extended-timescale simulations of rare events with rigorous kinetics using the weighted ensemble (WE) strategy.