本文主要介绍了增强采样外接软件PySAGES的基本安装和使用方法，重点是安装过程中没有写清楚的一些环境依赖和可能出现的问题介绍，以及相应的解决方案。并简单的梳理了一下PySAGES软件的工作流机制，其能够做到Zero Copy，并使得Enhanced Sampling不再成为很多模拟的Bottleneck，这是一个相当出色的结果。
技术背景
PySAGES是一款可以使用GPU加速的增强采样插件，它可以直接对接到OpenMM上进行增强采样分子动力学模拟，这里我们测试一下相关的安装，并尝试跑一个简单的增强采样示例。
安装PySAGES
PySAGES本身可以使用pip进行安装：
python3 -m pip install git+https://github.com/SSAGESLabs/PySAGES.git
$ python3 -m pip install git+https://github.com/SSAGESLabs/PySAGES.git
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看起来是安装成功了，跑一个简单的用例试一试。先准备一个简单的pdb文件：
input.pdb
CRYST1 0.000 0.000 0.000 90.00 90.00 90.00 P 1 1
ATOM 1 H1 ACE A 1 -1.838 -6.570 -0.492 0.00 0.00
ATOM 2 CH3 ACE A 1 -0.764 -6.587 -0.283 0.00 0.00
ATOM 3 H2 ACE A 1 -0.392 -7.533 -0.746 0.00 0.00
ATOM 4 H3 ACE A 1 -0.592 -6.446 0.740 0.00 0.00
ATOM 5 C ACE A 1 -0.006 -5.404 -0.828 0.00 0.00
ATOM 6 O ACE A 1 -0.544 -4.619 -1.673 0.00 0.00
ATOM 7 N ALA A 2 1.278 -5.323 -0.423 0.00 0.00
ATOM 8 H ALA A 2 1.622 -5.845 0.368 0.00 0.00
ATOM 9 CA ALA A 2 2.284 -4.164 -0.399 0.00 0.00
ATOM 10 HA ALA A 2 2.098 -3.653 0.505 0.00 0.00
ATOM 11 CB ALA A 2 3.651 -4.787 -0.566 0.00 0.00
ATOM 12 HB1 ALA A 2 4.274 -4.031 -0.972 0.00 0.00
ATOM 13 HB2 ALA A 2 3.977 -5.106 0.419 0.00 0.00
ATOM 14 HB3 ALA A 2 3.697 -5.612 -1.274 0.00 0.00
ATOM 15 C ALA A 2 1.995 -3.152 -1.576 0.00 0.00
ATOM 16 O ALA A 2 1.544 -2.065 -1.221 0.00 0.00
ATOM 17 N NME A 3 2.255 -3.614 -2.845 0.00 0.00
ATOM 18 H NME A 3 2.788 -4.485 -2.929 0.00 0.00
ATOM 19 CH3 NME A 3 1.991 -2.802 -4.055 0.00 0.00
ATOM 20 HH31 NME A 3 2.561 -1.891 -3.988 0.00 0.00
ATOM 21 HH32 NME A 3 1.897 -3.419 -4.937 0.00 0.00
ATOM 22 HH33 NME A 3 0.985 -2.388 -3.930 0.00 0.00
END然后在上一篇文章中介绍的OpenMM基础案例的基础上增加一个PySAGES的MetaDynamics案例：
from openmm.app import PDBFile, ForceField, Simulation, PDBReporter, StateDataReporter, HBonds
from openmm import LangevinMiddleIntegrator
from openmm.unit import nanometer, kelvin, picoseconds, picosecond, BOLTZMANN_CONSTANT_kB, AVOGADRO_CONSTANT_NA, kilojoules_per_mole
import pysages
from pysages.colvars import DihedralAngle
from numpy import pi
from pysages.methods import Metadynamics, MetaDLogger
kB = BOLTZMANN_CONSTANT_kB * AVOGADRO_CONSTANT_NA
kB = kB.value_in_unit(kilojoules_per_mole / kelvin)
def NVT(pdb_name='input.pdb', pdb_out='output.pdb', ff='amber14-all.xml', log_file='log.dat'):
pdb = PDBFile(pdb_name)
forcefield = ForceField(ff)
system = forcefield.createSystem(pdb.topology, nonbondedCutoff=1*nanometer, constraints=HBonds)
integrator = LangevinMiddleIntegrator(300*kelvin, 1/picosecond, 0.004*picoseconds)
simulation = Simulation(pdb.topology, system, integrator)
simulation.context.setPositions(pdb.positions)
simulation.minimizeEnergy()
simulation.reporters.append(PDBReporter(pdb_out, 1000))
simulation.reporters.append(StateDataReporter(log_file, 1000, step=True, potentialEnergy=True, temperature=True, volume=True))
return simulation
def MetaD(hills_file="hills.dat", time_steps=10000):
cvs = [DihedralAngle([4, 6, 8, 14]), DihedralAngle([6, 8, 14, 16])]
height = 1.2 # kJ/mol
sigma = [0.35, 0.35] # radians
deltaT = 5000
stride = 500
ngauss = time_steps // stride + 1
grid = pysages.Grid(lower=(-pi, -pi), upper=(pi, pi), shape=(50, 50), periodic=True)
method = Metadynamics(cvs, height, sigma, stride, ngauss, deltaT=deltaT, kB=kB, grid=grid)
callback = MetaDLogger(hills_file, stride)
run_result = pysages.run(method, NVT, time_steps, callback)
result = pysages.analyze(run_result)
metapotential = result["metapotential"]
return metapotential
if __name__ == '__main__':
potential = MetaD()
print (potential)发生了一个报错：
Traceback (most recent call last):
File "/home/dechin/projects/gitee/dechin/tests/test_openmm.py", line 43, in <module>
potential = MetaD()
File "/home/dechin/projects/gitee/dechin/tests/test_openmm.py", line 37, in MetaD
run_result = pysages.run(method, NVT, time_steps, callback)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/plum/function.py", line 383, in __call__
return _convert(method(*args, **kw_args), return_type)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 230, in run
futures = [submit_work(ex, method, callback) for _ in range(config.copies)]
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 230, in <listcomp>
futures = [submit_work(ex, method, callback) for _ in range(config.copies)]
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 218, in submit_work
return executor.submit(
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/utils.py", line 33, in submit
future.set_result(fn(*args, **kwargs))
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 324, in _run_replica
return run(method, *args, **kwargs)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/plum/function.py", line 383, in __call__
return _convert(method(*args, **kw_args), return_type)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 371, in _run
sampling_context = SamplingContext(method, context_generator, callback, context_args)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/backends/core.py", line 101, in __init__
backend = import_module("." + self._backend_name, package="pysages.backends")
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/importlib/__init__.py", line 126, in import_module
return _bootstrap._gcd_import(name[level:], package, level)
File "<frozen importlib._bootstrap>", line 1050, in _gcd_import
File "<frozen importlib._bootstrap>", line 1027, in _find_and_load
File "<frozen importlib._bootstrap>", line 1006, in _find_and_load_unlocked
File "<frozen importlib._bootstrap>", line 688, in _load_unlocked
File "<frozen importlib._bootstrap_external>", line 883, in exec_module
File "<frozen importlib._bootstrap>", line 241, in _call_with_frames_removed
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/backends/openmm.py", line 8, in <module>
import openmm_dlext as dlext
ModuleNotFoundError: No module named 'openmm_dlext'提示是需要安装一个openmm_dlext的插件。因为这个插件只有一个Github仓库，没有太多的文档，也没有介绍怎么安装的。我测试过下载源码下来，cmake&&make install去编译构建，但是又会有很多其他的报错提示要处理，最终我采取的方案是使用conda安装：
$ conda install conda-forge::openmm-dlext安装完成后再次运行上面的案例，又有一个新的报错：
$ python3 test_openmm.py
Traceback (most recent call last):
File "/home/dechin/projects/gitee/dechin/tests/test_openmm.py", line 43, in <module>
potential = MetaD()
File "/home/dechin/projects/gitee/dechin/tests/test_openmm.py", line 37, in MetaD
run_result = pysages.run(method, NVT, time_steps, callback)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/plum/function.py", line 383, in __call__
return _convert(method(*args, **kw_args), return_type)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 230, in run
futures = [submit_work(ex, method, callback) for _ in range(config.copies)]
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 230, in <listcomp>
futures = [submit_work(ex, method, callback) for _ in range(config.copies)]
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 218, in submit_work
return executor.submit(
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/utils.py", line 33, in submit
future.set_result(fn(*args, **kwargs))
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 324, in _run_replica
return run(method, *args, **kwargs)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/plum/function.py", line 383, in __call__
return _convert(method(*args, **kw_args), return_type)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 371, in _run
sampling_context = SamplingContext(method, context_generator, callback, context_args)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/backends/core.py", line 102, in __init__
self.sampler = backend.bind(self, callback, **kwargs)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/backends/openmm.py", line 194, in bind
force.add_to(context) # OpenMM will handle the lifetime of the force
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/openmm_dlext/__init__.py", line 29, in add_to
self.__alt__.add_to(_to_capsule(context), _to_capsule(system))
RuntimeError: Unsupported platform关于这个报错，我在openmm_dlext的Issue里面找到了相应的解决方案，说是要手动配置一下CUDA Platform，于是修改一下代码：
from openmm.app import PDBFile, ForceField, Simulation, PDBReporter, StateDataReporter, HBonds
from openmm import LangevinMiddleIntegrator, Platform
from openmm.unit import nanometer, kelvin, picoseconds, picosecond, BOLTZMANN_CONSTANT_kB, AVOGADRO_CONSTANT_NA, kilojoules_per_mole
import pysages
from pysages.colvars import DihedralAngle
from numpy import pi
from pysages.methods import Metadynamics, MetaDLogger
openmm_platform = Platform.getPlatformByName('CUDA')
kB = BOLTZMANN_CONSTANT_kB * AVOGADRO_CONSTANT_NA
kB = kB.value_in_unit(kilojoules_per_mole / kelvin)
def NVT(pdb_name='input.pdb', pdb_out='output.pdb', ff='amber14-all.xml', log_file='log.dat', platform=openmm_platform):
pdb = PDBFile(pdb_name)
forcefield = ForceField(ff)
system = forcefield.createSystem(pdb.topology, nonbondedCutoff=1*nanometer, constraints=HBonds)
integrator = LangevinMiddleIntegrator(300*kelvin, 1/picosecond, 0.004*picoseconds)
simulation = Simulation(pdb.topology, system, integrator, platform=platform)
simulation.context.setPositions(pdb.positions)
simulation.minimizeEnergy()
simulation.reporters.append(PDBReporter(pdb_out, 1000))
simulation.reporters.append(StateDataReporter(log_file, 1000, step=True, potentialEnergy=True, temperature=True, volume=True))
return simulation
def MetaD(hills_file="hills.dat", time_steps=10000):
cvs = [DihedralAngle([4, 6, 8, 14]), DihedralAngle([6, 8, 14, 16])]
height = 1.2 # kJ/mol
sigma = [0.35, 0.35] # radians
deltaT = 5000
stride = 500
ngauss = time_steps // stride + 1
grid = pysages.Grid(lower=(-pi, -pi), upper=(pi, pi), shape=(50, 50), periodic=True)
method = Metadynamics(cvs, height, sigma, stride, ngauss, deltaT=deltaT, kB=kB, grid=grid)
callback = MetaDLogger(hills_file, stride)
run_result = pysages.run(method, NVT, time_steps, callback)
result = pysages.analyze(run_result)
metapotential = result["metapotential"]
return metapotential
if __name__ == '__main__':
potential = MetaD()
print (potential)再次运行，又出现一个新的报错：
Traceback (most recent call last):
File "/home/dechin/projects/gitee/dechin/tests/test_openmm.py", line 44, in <module>
potential = MetaD()
File "/home/dechin/projects/gitee/dechin/tests/test_openmm.py", line 38, in MetaD
run_result = pysages.run(method, NVT, time_steps, callback)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/plum/function.py", line 383, in __call__
return _convert(method(*args, **kw_args), return_type)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 230, in run
futures = [submit_work(ex, method, callback) for _ in range(config.copies)]
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 230, in <listcomp>
futures = [submit_work(ex, method, callback) for _ in range(config.copies)]
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 218, in submit_work
return executor.submit(
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/utils.py", line 33, in submit
future.set_result(fn(*args, **kwargs))
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 324, in _run_replica
return run(method, *args, **kwargs)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/plum/function.py", line 383, in __call__
return _convert(method(*args, **kw_args), return_type)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 371, in _run
sampling_context = SamplingContext(method, context_generator, callback, context_args)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/backends/core.py", line 78, in __init__
context = context_generator(**context_args)
File "/home/dechin/projects/gitee/dechin/tests/test_openmm.py", line 20, in NVT
simulation = Simulation(pdb.topology, system, integrator, platform=platform)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/openmm/app/simulation.py", line 104, in __init__
self.context = mm.Context(self.system, self.integrator, platform)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/openmm/openmm.py", line 19511, in __init__
_openmm.Context_swiginit(self, _openmm.new_Context(*args))
openmm.OpenMMException: Error loading CUDA module: CUDA_ERROR_UNSUPPORTED_PTX_VERSION (222)好，这次是CUDA版本号不支持，类似的问题在一条openmm的issue中有讨论过，需要检查一下自己本地cudatoolkit的配置信息：
$ conda list | grep cudatoolkit
$这里发现在这个虚拟环境里面没有配置cudatoolkit，需要再装一个：
$ conda install -c conda-forge cudatoolkit=11.6
Collecting package metadata (current_repodata.json): done
Solving environment: failed with initial frozen solve. Retrying with flexible solve.
Collecting package metadata (repodata.json): done
Solving environment: done
==> WARNING: A newer version of conda exists. <==
current version: 23.1.0
latest version: 24.11.0
Please update conda by running
$ conda update -n base -c defaults conda
Or to minimize the number of packages updated during conda update use
conda install conda=24.11.0
## Package Plan ##
environment location: /home/dechin/anaconda3/envs/jax
added / updated specs:
- cudatoolkit=11.6
The following packages will be downloaded:
package | build
---------------------------|-----------------
cudatoolkit-11.6.2 | hfc3e2af_13 598.8 MB conda-forge
openmm-8.1.1 | py310h358ce72_1 10.8 MB conda-forge
openmm-dlext-0.2.1 | py310h552f1b7_8 115 KB conda-forge
------------------------------------------------------------
Total: 609.8 MB
The following NEW packages will be INSTALLED:
cudatoolkit conda-forge/linux-64::cudatoolkit-11.6.2-hfc3e2af_13
The following packages will be REMOVED:
cuda-nvrtc-12.4.127-h99ab3db_1
cuda-version-12.4-hbda6634_3
libcufft-11.2.1.3-h99ab3db_1
The following packages will be UPDATED:
openssl anaconda/pkgs/main::openssl-3.0.15-h5~ --> conda-forge::openssl-3.4.0-hb9d3cd8_0
The following packages will be SUPERSEDED by a higher-priority channel:
ca-certificates anaconda/pkgs/main::ca-certificates-2~ --> conda-forge::ca-certificates-2024.8.30-hbcca054_0
openmm anaconda/cloud/conda-forge::openmm-8.~ --> conda-forge::openmm-8.1.1-py310h358ce72_1
The following packages will be DOWNGRADED:
openmm-dlext 0.2.1-py310hcb41016_8 --> 0.2.1-py310h552f1b7_8
Proceed ([y]/n)? y
Downloading and Extracting Packages
Preparing transaction: done
Verifying transaction: done
Executing transaction: | By downloading and using the CUDA Toolkit conda packages, you accept the terms and conditions of the CUDA End User License Agreement (EULA): https://docs.nvidia.com/cuda/eula/index.html
done再次执行上面的程序，报错+1：
$ python3 test_openmm.py
Traceback (most recent call last):
File "/home/dechin/projects/gitee/dechin/tests/test_openmm.py", line 44, in <module>
potential = MetaD()
File "/home/dechin/projects/gitee/dechin/tests/test_openmm.py", line 38, in MetaD
run_result = pysages.run(method, NVT, time_steps, callback)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/plum/function.py", line 383, in __call__
return _convert(method(*args, **kw_args), return_type)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 230, in run
futures = [submit_work(ex, method, callback) for _ in range(config.copies)]
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 230, in <listcomp>
futures = [submit_work(ex, method, callback) for _ in range(config.copies)]
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 218, in submit_work
return executor.submit(
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/utils.py", line 33, in submit
future.set_result(fn(*args, **kwargs))
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 324, in _run_replica
return run(method, *args, **kwargs)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/plum/function.py", line 383, in __call__
return _convert(method(*args, **kw_args), return_type)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/methods/core.py", line 371, in _run
sampling_context = SamplingContext(method, context_generator, callback, context_args)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/backends/core.py", line 102, in __init__
self.sampler = backend.bind(self, callback, **kwargs)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/backends/openmm.py", line 197, in bind
helpers, restore, bias = build_helpers(sampling_context.view, sampling_method)
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/backends/openmm.py", line 135, in build_helpers
sync_forces, view = utils.cupy_helpers()
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/site-packages/pysages/backends/utils.py", line 21, in cupy_helpers
cupy = importlib.import_module("cupy")
File "/home/dechin/anaconda3/envs/jax/lib/python3.10/importlib/__init__.py", line 126, in import_module
return _bootstrap._gcd_import(name[level:], package, level)
File "<frozen importlib._bootstrap>", line 1050, in _gcd_import
File "<frozen importlib._bootstrap>", line 1027, in _find_and_load
File "<frozen importlib._bootstrap>", line 1004, in _find_and_load_unlocked
ModuleNotFoundError: No module named 'cupy'不过这个看起来好处理，就是少装了一个cupy的依赖，稳妥起见，我们还是选择使用conda来安装cupy：
$ conda install -c conda-forge cupy -y
Collecting package metadata (current_repodata.json): done
Solving environment: failed with initial frozen solve. Retrying with flexible solve.
Solving environment: -
failed with repodata from current_repodata.json, will retry with next repodata source.
Collecting package metadata (repodata.json): done
Solving environment: done
==> WARNING: A newer version of conda exists. <==
current version: 23.1.0
latest version: 24.11.0
Please update conda by running
$ conda update -n base -c defaults conda
Or to minimize the number of packages updated during conda update use
conda install conda=24.11.0
## Package Plan ##
environment location: /home/dechin/anaconda3/envs/jax
added / updated specs:
- cupy
The following packages will be downloaded:
package | build
---------------------------|-----------------
cuda-version-11.6 | hca96458_3 21 KB conda-forge
cupy-13.3.0 | py310h189a05f_2 347 KB conda-forge
cupy-core-13.3.0 | py310h5da974a_2 42.9 MB conda-forge
fastrlock-0.8.2 | py310hc6cd4ac_2 37 KB conda-forge
------------------------------------------------------------
Total: 43.3 MB
The following NEW packages will be INSTALLED:
cuda-version conda-forge/noarch::cuda-version-11.6-hca96458_3
cupy conda-forge/linux-64::cupy-13.3.0-py310h189a05f_2
cupy-core conda-forge/linux-64::cupy-core-13.3.0-py310h5da974a_2
fastrlock conda-forge/linux-64::fastrlock-0.8.2-py310hc6cd4ac_2
Downloading and Extracting Packages
Preparing transaction: done
Verifying transaction: done
Executing transaction: done然后再执行测试程序：
$ python3 test_openmm.py
<CompiledFunction of <function analyze.<locals>.<lambda> at 0x7fc1a04aba30>>同时会在执行路径下生成log.dat文件和hills.dat文件如下：
log.dat
#"Step","Potential Energy (kJ/mole)","Temperature (K)","Box Volume (nm^3)"
1000,-39.254608154296875,284.2437497410935,8.0
2000,-18.68511962890625,318.9596355900776,8.0
3000,-30.86761474609375,289.998240351891,8.0
4000,-21.921295166015625,338.6328004320157,8.0
5000,-31.451812744140625,245.66209355694957,8.0
6000,-32.077880859375,182.1505555238515,8.0
7000,-56.050750732421875,252.68200201473644,8.0
8000,-27.819427490234375,289.4957194622587,8.0
9000,-36.86553955078125,271.0313362334861,8.0
10000,-12.531005859375,254.41902934626566,8.0 hills.dat
500 -1.3592318296432495 1.5952203273773193 0.35 0.35 1.2
1000 -1.1732323169708252 0.8145138621330261 0.35 0.35 1.1973907824735082
1500 -1.433311104774475 1.7097197771072388 0.35 0.35 1.1671557288100634
2000 -1.114228367805481 2.042632579803467 0.35 0.35 1.179103510697602
2500 -1.1403875350952148 0.9936402440071106 0.35 0.35 1.1603072043059584
3000 -1.2672390937805176 0.40286365151405334 0.35 0.35 1.173835519022326
3500 -1.302258014678955 1.4455255270004272 0.35 0.35 1.1211946752964734
4000 -1.4070658683776855 1.013744592666626 0.35 0.35 1.121531633082655
4500 -2.6735711097717285 2.6055266857147217 0.35 0.35 1.1999969285502206
5000 -2.8140780925750732 2.9895386695861816 0.35 0.35 1.1809462925907876
5500 -2.6453146934509277 2.5226593017578125 0.35 0.35 1.1505253387717271
6000 -2.476658344268799 2.7877397537231445 0.35 0.35 1.1410532890823843
6500 -2.7321791648864746 -2.84220814704895 0.35 0.35 1.1797609616409976
7000 -1.596192479133606 1.0611979961395264 0.35 0.35 1.1126547940366505
7500 -1.3219820261001587 0.2645364999771118 0.35 0.35 1.1460450294138773
8000 -1.5232703685760498 1.4845924377441406 0.35 0.35 1.0865578670844307
8500 -1.3037762641906738 0.6937571167945862 0.35 0.35 1.076390175717164
9000 -1.3598891496658325 2.0672760009765625 0.35 0.35 1.1276490649082718
9500 -2.420367479324341 2.7348878383636475 0.35 0.35 1.1032026693365438喜大普奔，PySAGES环境部署完毕！
案例测试
还是沿用上面的input.pdb案例，这里我们测试一个MetaDynamics的FES，增加了一个analyse的plot模块：
from openmm.app import PDBFile, ForceField, Simulation, PDBReporter, StateDataReporter, HBonds
from openmm import LangevinMiddleIntegrator, Platform
from openmm.unit import nanometer, kelvin, picoseconds, picosecond, BOLTZMANN_CONSTANT_kB, AVOGADRO_CONSTANT_NA, kilojoules_per_mole
from sys import stdout
import pysages
from pysages.colvars import DihedralAngle
from numpy import pi
from pysages.methods import Metadynamics, MetaDLogger
from pysages.approxfun import compute_mesh
import matplotlib.pyplot as plt
openmm_platform = Platform.getPlatformByName('CUDA')
kB = BOLTZMANN_CONSTANT_kB * AVOGADRO_CONSTANT_NA
kB = kB.value_in_unit(kilojoules_per_mole / kelvin)
T = 300*kelvin
dt = 0.004*picoseconds
def NVT(pdb_name='input.pdb', pdb_out='output.pdb', ff='amber14-all.xml', log_file='log.dat', platform=openmm_platform):
pdb = PDBFile(pdb_name)
forcefield = ForceField(ff)
system = forcefield.createSystem(pdb.topology, nonbondedCutoff=1*nanometer, constraints=HBonds)
integrator = LangevinMiddleIntegrator(T, 1/picosecond, dt)
simulation = Simulation(pdb.topology, system, integrator, platform=platform)
simulation.context.setPositions(pdb.positions)
simulation.minimizeEnergy()
simulation.reporters.append(PDBReporter(pdb_out, 1000))
simulation.reporters.append(StateDataReporter(stdout, 1000, step=True, potentialEnergy=True, temperature=True, volume=True))
simulation.reporters.append(StateDataReporter(log_file, 1000, step=True, potentialEnergy=True, temperature=True, volume=True))
return simulation
def plot_grid(metapotential, method):
plot_grid = pysages.Grid(lower=(-pi, -pi), upper=(pi, pi), shape=(64, 64), periodic=True)
xi = (compute_mesh(plot_grid) + 1) / 2 * plot_grid.size + plot_grid.lower
alpha = (
1
if method.deltaT is None
else (T.value_in_unit(kelvin) + method.deltaT) / method.deltaT
)
kT = kB * T.value_in_unit(kelvin)
A = metapotential(xi) * -alpha / kT
A = A - A.min()
A = A.reshape(plot_grid.shape)
# plot and save free energy to a PNG file
fig, ax = plt.subplots(dpi=120)
im = ax.imshow(A, interpolation="bicubic", origin="lower", extent=[-pi, pi, -pi, pi])
ax.contour(A, levels=12, linewidths=0.75, colors="k", extent=[-pi, pi, -pi, pi])
ax.set_xlabel(r"$\phi$")
ax.set_ylabel(r"$\psi$")
cbar = plt.colorbar(im)
cbar.ax.set_ylabel(r"$A~[k_{B}T]$", rotation=270, labelpad=20)
fig.savefig("Figure.png", dpi=fig.dpi)
def MetaD(hills_file="hills.dat", time_steps=50000):
cvs = [DihedralAngle([4, 6, 8, 14]), DihedralAngle([6, 8, 14, 16])]
height = 2.0 # kJ/mol
sigma = [0.2, 0.2] # radians
deltaT = 5000
stride = 50
ngauss = time_steps // stride + 1
grid = pysages.Grid(lower=(-pi, -pi), upper=(pi, pi), shape=(50, 50), periodic=True)
method = Metadynamics(cvs, height, sigma, stride, ngauss, deltaT=deltaT, kB=kB, grid=grid)
callback = MetaDLogger(hills_file, stride)
run_result = pysages.run(method, NVT, time_steps, callback)
result = pysages.analyze(run_result)
metapotential = result["metapotential"]
plot_grid(metapotential, method)
return result
if __name__ == '__main__':
res = MetaD()因为在OpenMM的Simulation的Report中我们增加了一个stdout，因此会同时在屏幕上输出结果，也会在相应的log.dat文件中保存结果，运行输出如下：
#"Step","Potential Energy (kJ/mole)","Temperature (K)","Box Volume (nm^3)"
1000,9.73681640625,377.6993364201515,8.0
2000,-23.971282958984375,298.44721588786604,8.0
3000,-15.113677978515625,213.76058649837066,8.0
4000,-9.906219482421875,444.7447921758242,8.0
5000,-35.83831787109375,299.89809403902336,8.0
6000,-33.826202392578125,313.4731859605099,8.0
7000,-19.394073486328125,337.10699269365875,8.0
8000,-45.882415771484375,250.66251735991736,8.0
9000,-14.17413330078125,358.22016011687015,8.0
10000,-29.421051025390625,246.90072858113598,8.0
11000,-19.7567138671875,301.9975514069083,8.0
12000,-32.948822021484375,367.195135668361,8.0
13000,-9.27825927734375,289.7929305791173,8.0
14000,-30.180389404296875,309.66557282887885,8.0
15000,-2.736083984375,302.5309003205113,8.0
16000,-32.576629638671875,291.86829747083937,8.0
17000,-14.334503173828125,231.850481046364,8.0
18000,-20.755645751953125,298.57497669296873,8.0
19000,-43.75299072265625,306.65343794873587,8.0
20000,33.35467529296875,258.82936068957366,8.0
21000,-1.04156494140625,339.65646518408494,8.0
22000,0.01190185546875,197.8572390770094,8.0
23000,5.273040771484375,289.2310517046787,8.0
24000,-14.901947021484375,383.9835521646287,8.0
25000,-0.839019775390625,268.7104144595147,8.0
26000,-23.747772216796875,222.84395037451839,8.0
27000,-27.284759521484375,285.9093985100245,8.0
28000,-23.12164306640625,248.21416090812198,8.0
29000,10.6822509765625,319.4106894537426,8.0
30000,-16.64678955078125,304.24748131130184,8.0
31000,-6.5423583984375,329.8362141299685,8.0
32000,-3.944793701171875,333.3584976075751,8.0
33000,-29.894744873046875,355.53462625307105,8.0
34000,-22.54876708984375,366.93298893561547,8.0
35000,-14.81097412109375,330.12835522481674,8.0
36000,-45.39825439453125,363.9047710837139,8.0
37000,-5.33160400390625,355.4129749973852,8.0
38000,-19.806365966796875,361.73243838698073,8.0
39000,-13.85650634765625,411.9526625662002,8.0
40000,1.711639404296875,225.61063301965956,8.0
41000,-34.70196533203125,389.73863301467037,8.0
42000,-33.63153076171875,307.1604571229406,8.0
43000,-37.86602783203125,277.5274210978626,8.0
44000,-3.5263671875,248.0723224072663,8.0
45000,21.574676513671875,294.5427172838524,8.0
46000,-31.097808837890625,302.0992611330069,8.0
47000,-23.125152587890625,307.7661366778404,8.0
48000,8.406402587890625,174.53798831979185,8.0
49000,-19.694549560546875,380.88297517197196,8.0
50000,12.754608154296875,380.40854584876394,8.0这里输出的FES被保存成了一个图片，内容为：
这就是PySAGES的Well-Tempered MetaDynamics输出的FES结果。
工作流
PySAGES的工作流是这样的：
这里我们的backend使用的就是OpenMM了，大致的流程是，通过PySAGES来构建对应backend的Simulation对象，然后启动Simulation。每一次需要update bias force的时候，从backend传回来一个force，在PySAGES层面加入bias force然后传回backend。循环迭代，直至time step截止。
PySAGES自带了一些增强采样的方法和一些定义好的CV，当然，因为其基于Jax-Python开发，因此自定义一个新的CV在形式上也非常的简洁：
最关键的，一般这种外接的增强采样软件会很大程度上影响到整体分子模拟的性能，甚至很可能成为Bottleneck。而根据PySAGES官方给出的profile结果来看：
MetaDynamics部分的时间占比并没有成为Bottleneck，从时长比例上来说，这个性能表现是非常突出的。
总结概要
本文主要介绍了增强采样外接软件PySAGES的基本安装和使用方法，重点是安装过程中没有写清楚的一些环境依赖和可能出现的问题介绍，以及相应的解决方案。并简单的梳理了一下PySAGES软件的工作流机制，其能够做到Zero Copy，并使得Enhanced Sampling不再成为很多模拟的Bottleneck，这是一个相当出色的结果。
版权声明
作者ID：DechinPhy
参考链接
