Release history¶

This section features and improvements of note in each release.

The full release history can be viewed at the GitHub yank releases page.

0.23.4 Bugfix release¶

Fix bug #1012 when determining automatically the group_size of replica exchange simulations with MPI (#1073).
Fix bug where passing WT to the modeller directive caused the automatic setup pipeline to crash (#1074).

0.23.3 Adds support for single mutations using Modeller¶

Adds an optional modeller` directive to the ``molecules section of the YAML file through Modeller, a tool for comparative modeling of protein structures.
The following options are accessible through the modeller directive. (docs)
- apply_mutations: Specify protein single mutations (e.g., T315I). (docs)

0.23.2 More Multi-Experiment Cleanup¶

resume_setup and resume_experiment are True by default
Fixed bug where yank analyze extract-trajectory could not be executed
Further updated multi-analysis docs to reflect multi-experiment changes

0.23.1 Multi-Experiment and Online Bug¶

Fixed bug in MultiExperimentAnalyzer where a path ending in the folder separator (e.g. /) caused all files to write to the same place.
Fixed bug where increasing number of iterations did not continue experiment if online analysis was turned on and previously hit the max number of iterations
Fixed bug where online analysis and harmonic unbiasing caused MBAR to not form due to misformed initial_f_k
MultiExperimentAnalyzer now gracefully traps an error caught by one experiment without crashing others
Fixed bug in MultiStateReporter when there were unsampled thermodynamic states as end-states but they referenced sampled thermodynamic states for their standard system

0.23.0 Multi-Analysis¶

Added new ExperimentAnalyzer class as API call for auto_analyze like functions. Supports serialized output to Pickle
Added new MultiExperimentAnalyzer class to analyze all experiments found in a YAML input file with the ExperimentAnalyzer. Supported by MPI for parallel action
Unified all auto_analyze like objects to go through the ExperimentAnalyzer, such as the API and Jupyter Notebook calls
Existing API calls should remain unchanged and serve as pass-throughs to the new classes
Major changes to the CLI behavior of yank analyze and yank analyze report to support the new features. These should not affect existing code, only support new features.
Fixed bug in yank selftest with the OpenEye tests. Also silenced the OpenEye internal tests due to time. Dependency checks are still active
Update API docs

0.22.3 Balance Checkpoint with IO¶

Reduced default checkpoint interval to 50 (was 200) to balance disk IO time with time between checkpoints
Fixed bug in DSL selection string from YAML

0.22.2 Topography Property Copy¶

Critical bug fix for Topology where ions of charged ligands were considered part of the ligand
Online analysis MBAR failures can no longer halt simulations
Added ability for analyze CLI (--fulltraj) and API (use_full_trajectory=True) to force use the full trajectory

0.22.1 Online Analysis Default¶

Online analysis will always run by default now, with no target error, run every checkpoint interval, and with at least 200 iterations
Online analysis can now be a set to the checkpoint interval by setting online_analysis_interval: "checkpoint" in the YAML files (application layer, not API)
Checkpoint interval increased from default of 10 to 200
Analysis now uses the online-analysis data if available by default

0.22.0 RMSD the Casbah¶

Enhancements and features¶

Added RMSD Type restraint, requires OpenMM 7.3 or greater to access. You can have older versions of OpenMM, but this feature is unavailable and will raise a graceful error should you attempt to use it.
Added more robust last good iteration saving
Added more robust restore from checkpoint access
Exposed checkpoint interval iterations in MultiStateReporter
Generalized the Boresch restraints to a BoreschLike restraint to support new energy functions.
Boresch restraint automatic atom selection now picks bonded heavy atoms
Boresch restraints no longer accept standard_state_correction_method as an option
Added new Haversined Torsion Boresch Torsion (PeriodicTorsionBoresch) Boresch-like restraint where functional form of torsion is periodic support more numerically stable energy functions
Changed the timeseries analysis to only consider a maximum number of points on which to evaluate “is this equilibrium” to speed up process.
Implement #848 Use MDTraj Trajectory.save() method instead of inferring function from extension.
Implement #635 Allow extract-trajectory to handle trajectories with 1 frame.

Bugfixes¶

Fix bug #941 where unbiasing the restraint would crash the analysis if using a 32-bit OpenCL platform.
Fix bug #945 where relative imports of OpenEye tools would cause problems on some systems.
Temporarily pinned NetCDF4 to 1.3.1 until we can fix the bug introduced in 1.4.0 where masked arrays are always returned. This pin will be lifted in future releases.
Fix a bug where max_n_iterations was ignored when computing the mixing statistics of the calculation (PR #963).
Fix bug #944 where ReplicaExchange.create() did not accept a single SamplerState anymore.
Fix a bug where the box vectors of SamplerStates were initialized incorrectly in MultiStateSampler.create() for NVT calculations (PR #969).
Fix bug #964 where using the state index argument in extract_trajectory with SAMS calculations would cause a crash.

0.21.2 More Post-Sams Bugfixes¶

Fix analysis on 32-bit platforms OS agnostic
More robust analysis tests
Pin Cerberus to 1.1 as 1.2 breaks some schemas. Proper fix in a later version.
UML Diagrams added to docs
Fix API bug for resuming simulations without specifying how many iterations to run

0.21.1 Post-SAMS Bugfixes¶

Fix bug in FIRE minimizer logging
Fix Cray environment variables
Make tests more robust to undersampled analysis results
Fix molecule imaging incorrectly in trajectory extraction

0.21.0 SAMS and General Multistate Samplers¶

This release represents a major change in the YANK codebase.

Summary of Release¶

YANK’s sampling scheme now has a generalized scheme and runs on one of three primary samplers:

MultiStateSampler: Fixed state sampler where no states mix
ReplicaExchange: Dense state sampling with state swapping each iteration
ParallelTempering: Special extension of ReplicaExchange which swaps temperatures, with more efficient energy evaluation
SAMSSampler: Self-Adjusted Mixture Sampling [21], Single replica sampler which dynamically samples all thermodynamic states with long enough run time

The samplers are now part of the YANK multistate module and will eventually be ported to OpenMMTools. The YAML syntax has been extended that two new sections can be specified: MCMC Moves, and Samplers. These are fully optional blocks which default to a specific set if not specified. Several old YAML options like number_of_iterations have been moved to the samplers block and replaced with default_X where X is the old setting name.

The old scheme of the single repex.py file housing all sampler and reporter information has been removed and the entire multistate module is designed to be extended and experimented with. Similarly, much of the old analyze.py module has been migrated to multistate and can be extended as well.

Detailed Changes¶

Generalize the Sampler framework into a new multistate module and generalized sampler class structure
Analysis suite now general and part of multistate with additional YANK-specific extensions in YANK’s analyze.py module
Analysis energies have been converted from old u_kln format to u_kn formalism
Test suites for samplers refactored to be general and test all samplers
Test suites for analysis refactored to be general and test all samplers
Samplers now operate on concept of neighborhood to determine which thermodynamic states the energy of a sample was evaluated at
Cleaned up language in “replica” (sampler), “state” (thermodynamic state), and “sample” (drawn from replica)
Improved online analysis in samplers with general I/O functions in reporter
Python notebooks now can serialize their data
Added notebook feature to do a free energy trace trying to converge free energies by progressively truncating more data from front and back
Restraint factories improved and redundant code cleaned up
Generalized utilities for checking function calls
Improved storage read speads by chunking HDF5 data to use the checkpoint interval for per-iteration instead of each iteration
Dependencies now defined purely by Conda meta.yaml and no longer through setup.py. Pip can no longer check for dependencies because of this
Added ability to unbias harmonic restraints during analysis
mcmc block added to the YAML syntax
samplers block added to the YAML syntax
Improved resuming boot up times by requiring newer OpenMMTools features
Renamed global option number_of_iterations to default_number_of_iterations. (docs)
Renamed global option timestep to default_timestep. (docs)
Renamed global option nsteps_per_iteration to default_nsteps_per_iteration. (docs)
The global options collision_rate, mc_displacement_sigma, and integration_splitting are not supported anymore, but they can still be specified in the mcmc_moves` block.
Added support for automatic determination of processes_per_experiment (now the default). (docs)
Simulation minimization tries FIRE Minimizer [26] first before falling back to L-BFGS.
Fixed bug in Boresch restraints where atoms were not correctly re-randomized when initial pick is numerically unstable

0.20.1 Alchemical factory options and fast computation of the energy matrix¶

Allow user to specify options for openmmtools.alchemy.AbsoluteAlchemicalFactory in the YAML file. In particular, this introduces exact treatment of PME electrostatics for charged ligands. (docs)
Major optimization of the computation of the energy matrix.
Added the option max_n_contexts. (docs)
Bumped minimum required version of openmmtools to 0.14.0.

0.20.0 Support for processing proteins through PDBFixer¶

Adds an optional pdbfixer directive to the molecules section of the YAML file through PDBFixer, a simple OpenMM-based protein structure processing tool.
The following options are accessible through the pdbfixer directive. (docs)
- replace_nonstandard_residues: Replace nonstandard amino acids. (docs)
- remove_heterogens: Remove heterogens (such as ligands and waters). (docs)
- add_missing_residues: Add missing residues from the SEQRES block. (docs)
- add_missing_atoms: Add missing heavy atoms. (docs)
- apply_mutations: Specify protein mutations (e.g., T315I). (docs)

0.19.4 Schema and Parallel Setup Fixes¶

Fixed bug in parallel molecule setup which caused the same molecule to be setup multiple times.
Fixed bug in Cerberus schema for LEaP where molecule parameters accumulated.
Fixed bug where options in experiment section were not coerced.
Fixed status command to print information about all combinatorial experiments.
Faster restart with combinatorial experiments.

0.19.3 Support for Amber restart files¶

Added support for Amber rst7 files in phase1_path/phase2_path.
The CLI option jobid now uses 1-based numbering like Torque and LSF do for array jobs.

0.19.2 Include ions in solute-only trajectory¶

Ions are now included in the solute-only trajectories.

0.19.1 Trailblaze fix and restart stability from OpenMMTools¶

OpenMMTools 0.13.4 now required to fix issues listed below
Restrained atoms to absolute coordinates caused issue in Trailblaze with a Barostat
Last restart attempt uses a slower, but more robust restart method

0.19.0 Regions, Cerberus, and Errors¶

Added custom region selection to Topography
Custom regions can now be defined through YAML
Compound custom Topography regions can now be selected
Restraints atom selection can now use Topography Regions
Topography now can select from arbitrary string, either complex regions, DSL strings, and in the future SMARTS strings
Changed to Cerberus for data validation (was Schema), public facing validation schemas in the future
Added better error handling of known LEaP Errors
Fixed issue for start_frame and end_frame were ignored for trajectory extraction
OpenMMTools 0.13.3 now required to fix bug in SamplerState

0.18.0 Python 2 Dropped, Solute Only Trajectories, and Trailblaze Bugfixes¶

Python 2.X Support officially removed
Additional doc cleanups
Added restraint selection flowchart to documentation
Implement #772: Use infinity instead of None to specify unlimited number of iterations.
Implemented #557: Parallelized setup of molecules and systems with MPI.
Generalized restrained atoms selection during trailblaze scheme to include non-protein receptors (see also choderalab/openmmtools#290).
Fix loading of leap parameters from a local .dat files (allow us to use local versions of gaff parameters for validation).
Fix #762: Trailblaze protocol crashes with MPI.
Fixed bug when computing reduced potentials of simulated energies during trailblaze scheme.
Fix #763: Automatic path is saved in YAML as a mix of python and numpy floats.
Fixed the number of neutralizing counterions when receptor and ligand have opposite charges (we were adding too many in this case).
Fixed the log file name with lists of experiments that ended up being just .log.
Implemented workaround for fixing the net charge of cyclic multi-residue mol2 files.
Added GAFF2 Torsion support based on YAML input files
Solute-only trajectories can now be stored every iteration, regardless of checkpoint interval

0.17.0 Auto Alchemical Path and Split Langevin Integrators¶

Added Langevin Splitting Integrator which allows time-substep operation order
Automatic Alchemical Path selection feature added.
Many Website additions and cleanups
Online analysis allowing simulations to be run until they reach a target free energy uncertainty
Renamed and refactored YAMLBuilder to more general ExperimentBuilder
Remove ligand rotation and displacement with Boresch restraints to improve acceptance rates
Analyze module fully tested now
Fully updated API docstrings. API auto-generated on website
Parallelize multiple experiments over MPI by splitting MPI Communicator
Anisotropic dispersion options in YAML reduced to single option
Ionic Strength ability added to setup pipeline
Centroids for restraints now selectable through DSL string instead of whole molecule
Added MDTraj, Matplotlib, and Jupyter as requirements
Analyze Jupyter Notebooks can now be exported as pre-rendered static HTML or PDF pages (LaTeX required for PDF)
Refactor some API function names and keywords

0.16.2 Startup Speed and Reduced File Sizes¶

Automatic Expanded Cutoff Distance Selection
Compressed stored systems drastically reduce initial file sizes
Use C Yaml Dumper and Loaders to speed up YAML object processing
Requires OpenMMTools 0.11.2 at minimum

0.16.1 Auto Expanded Cutoffs and bug fixes for Transition Matrix and Reporter¶

Expanded cutoff now able to be chosen automatically instead of just hard coded number
Fixes bug causing transition matrix to be computed incorrectly, uses empirical to estimate
Allows user to drop samples equilibration report to avoid plot scale being dominated by initial fast equilibration

0.16.0 Full API and Python 3.6¶

Full feature API for setting up, running, and analyzing experiments
Supports new generalized MCMC moves, ThermodynamicStates, and other features from improved OpenMMTools
Checkpoint feature added to reduce file size, add portability to data analysis files.
Simulations can now alternate between phases to allow analysis even before simulations are done
OpenEye features compartmentalized so you don’t need every OpenEye feature YANK could use to use any of them
Major under the hood speed ups to base code and MPI behavior, includes a full code refactor.
Mol2 files can now read in multi-molecule files
No longer uses standalone Alchemy module, uses the one built into OpenMMTools
Added Python 3.6 support.
Retired Python 3.4 support

0.15.2 Health Report and Anisotropic Dispersion Control¶

Added simulation Health Report through a Jupyter Notebook with CLI support
Added ability to control Anisotropic Dispersion Correction through YAML files

0.15.0 Backend and Helpful Debugging Build¶

Added support for solvent_dsl in user defined systems of YAML pages
Removed Command Line Interface ability to do yank prepare and yank run
Added ability to overwrite individual YAML commands from command line
Added YAML feature to extend_simulation without modifying YAML files or command line every iteration
NaN’s generated during simulations serialize system, state, and integrator which can be passed off for debugging to others
Backend website updating and pushes improved
Improved GROMACS extension file handling

0.14.1 Early Access of 1.0 Release¶

YAML Syntax Structure Frozen. YANK YAML Version 1.0. All YAML scripts from this version will be compatible with future versions until YAML 2.0 New features may appear in the time meantime, but scripts will be forwards compatible.
Initial support for OpenMM XML systems and PDB files
Support for separate solvent configurations for the two phases when defined from amber/gromacs/openmm files
clearance in YAML now mandatory parameter of explicit solvent, but only when molecule setup goes through pipeline
Boresch Orientational Restraints fully implemented and documented.
Long range anisotropic dispersion correction improved to work on both ends of thermodynamic cycle leg
Documentation updated with better algorithms and theory sections.
Full walkthroughs of yank-examples added to online documentation
Various other documentation improvements
Support for upcoming OpenMM 7.1 Release and features (still works with 7.0.1)
YANK now on MIT License
Many bugfixes

0.12.0 (development)¶

Examples split into their own repository
Old CLI commands staring depreciation

0.11.2 (development)¶

Better long range dispersion and electrostatics corrections
Best practices and guidelines for the YAML documentation published

0.11.0 (development)¶

Full YAML documentation available online with all possible options specified
Developer documentation

0.10.0 (development)¶

Python 3.X support
Online documentation has been updated to include the YAML input files
Selftests now provide more helpful output

0.9.0 (development)¶

Changed YAML Syntax
New Command yank analyze extrat-trajectory to extract data from NetCDF4 file in a common trajectory format.
Support for solvation free energy calculations.
Automatic detection of MPI.
Various bug fixes.

0.8.0 (development)¶

alchemy split to a standalone repository
YAML based input files for setting up and running simulations. Uses an AmberTools-based pipeline

0.7.0 (development)¶

Convert to single Context Hamiltonian Replica Exchange

v0.6.1 (development)¶

mpi4py automatically installed via conda

v0.6.0 (development)¶

New command-line interface
Sphinx-based documentation

v0.5.0 (development)¶

Release for deployment to collaborators