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README.md

README.md

OpenMM SDM workflow

VERSION 0.2.0

A workflow to setup Single Decoupling alchemical binding free energy calculations with OpenMM.

Contributors

Emilio Gallicchio egallicchio@brooklyn.cuny.edu

Rajat Pal rajatfor2014@gmail.com

Sheenam Sheenam ssheenam@gradcenter.cuny.edu

License

This software is released under the LGPL license.

Credits

This software is maintained by the Gallicchio's laboratory at Department of Chemistry of Brooklyn College of CUNY (compmolbiophysbc.org). Development and maintenance of this software is supported in part from a grant from the National Science Foundation (CAREER 1750511).

Documentation and Tutorials

The documentation is organized in a set of tutorials. Currently, follow the T4 Lysozyme tutorial which prepares SDM calculations for farm of GPUs whether local or distributed on multiple servers. More tutorials are being finalized.

References

For a background on the alchemical process and the conformational sampling techniques used with SDM, consult our publications. Here are some key ones:

Installation

SDM calculations require several pieces of software:

  1. Conda 2
  2. OpenMM 7.2 or later
  3. Desmond DMS file reader for OpenMM
  4. Desmond (for force field parameter assignment)
  5. Msys
  6. SDM workflow
  7. SDM OpenMM plugin
  8. AGBNP OpenMM plugin
  9. ASyncRE for OpenMM
  10. UWHAM for R
  11. VMD for visualization

We summarize here the steps to install them and configure them. The steps below were tested on a 16.04 Ubuntu system.

Conda 2

Python bindings for OpenMM and other libraries are best stored in a Conda environment. We recommend the Miniconda 2 environment:

wget https://repo.anaconda.com/miniconda/Miniconda2-latest-Linux-x86_64.sh
bash Miniconda2-latest-Linux-x86_64.sh

In this tutorial we assume that Miniconda 2 is installed under $HOME/miniconda2. Adjust as needed.

Activate the conda environment

source ~/miniconda2/bin/activate

OpenMM

We recommend installing OpenMM from source since most of the steps required are the same as for building the SDM-related plugins (see below). However binary installations of OpenMM should probably also work. Detailed building instructions for OpenMM are here. SDM requires an OpenCL platform with GPUs from NVIDIA (CUDA) or AMD, which we assume are in place.

These are the steps we used to build OpenMM 7.3.1 on an Ubuntu 16.04 system:

mkdir $HOME/devel
cd $HOME/devel
wget https://github.com/pandegroup/openmm/archive/7.3.1.tar.gz
tar zxvf 7.3.1.tar.gz
conda install cmake=3.6.3 swig numpy
conda install -c conda-forge doxygen
mkdir build_openmm
cd build_openmm
ccmake -i ../openmm-7.3.1

Hit c (configure) until all variables are correctly set. Set CMAKE_INSTALL_PREFIX to point to the openmm installation directory. Here we assume $HOME/local/openmm-7.3.1. If an OpenCL platform is detected (such as from a NVIDIA CUDA installation) it will be enabled automatically. For the present purposes the CUDA platform is optional. Hit g to generate the makefiles and q to exit ccmake, then:

make install
make PythonInstall

The OpenMM libraries and header files will be installed in $HOME/local/openmm-7.3.1

Desmond File Reader for OpenMM

SDM uses Desmond DMS-formatted files. OpenMM includes a python library to load molecular files in DMS Desmond format however, the version of the Desmond file reader required for SDM is not yet included in the latest OpenMM sources. To patch the 7.3.1 OpenMM installation above with the latest DMS file reader do the following:

cd $HOME/devel
wget https://raw.githubusercontent.com/egallicc/openmm/master/wrappers/python/simtk/openmm/app/desmonddmsfile.py
cp desmonddmsfile.py $HOME/devel/openmm-7.3.1/wrappers/python/simtk/openmm/app/
cd $HOME/devel/build_openmm
make install
make PythonInstall

The sqlitebrowser application is very useful to inspect DMS files.

Desmond

In this tutorial we will use academic Desmond as part of the Schrodinger's environment to assign OPLS2005 force field parameters. Download and install Maestro/Desmond. If you have it, the commercial version of Maestro/Desmond also works, of course.

Msys

msys is a software package developed by DE Shaw Research to manipulate molecular structures. We use it to convert Maestro-formatted files to DMS-formatted files. Installation instructions are in Appendix A below. We assume that msys is installed in $HOME/local and that executables and libraries there are in the shell search paths. See Appendix A.

SDM Workflow

It's this package

cd $HOME/devel
git clone https://github.com/egallicc/openmm_sdm_workflow.git

For this tutorial we will use the structures stored under openmm_sdm_workflow/tutorial and modify the files under openmm_sdm_workfklow/tutorial/scripts to setup the simulations.

SDM OpenMM plugin

This is a plugin that implements a customized Langevin integrator to compute the alchemical potential in SDM.

cd $HOME/devel
git clone https://github.com/rajatkrpal/openmm_sdm_plugin.git

then follow the installation instructions for this package. Point the CMAKE_INSTALL_PREFIX and OPENMM_DIR to the OpenMM installation directory ($HOME/local/openmm-7.3.1 in this example).

AGBNP OpenMM plugin

This is a plugin that implements the AGBNP implicit solvent model in OpenMM

cd $HOME/devel
git clone https://github.com/egallicc/openmm_agbnp_plugin.git

then follow the installation instructions for this package. Point the CMAKE_INSTALL_PREFIX and OPENMM_DIR to the OpenMM installation directory ($HOME/local/openmm-7.3.1 in this example).

ASyncRE for OpenMM

ASyncRE is a package written in python to perform replica exchange simulations in asynchronous mode across a wide range of computational devices and grids. The specific version used by SDM distributes OpenMM jobs across GPU compute servers through passwordless ssh. To install it do:

conda install numpy configobj paramiko
cd $HOME/devel
git clone https://github.com/egallicc/async_re-openmm.git
cd async_re-openmm
python setup.py install

Here is a guide to set up password-less ssh across a farm of computers. ASyncRE does not require that the compute servers share a common user space and a shared filesystem.

UWHAM for R

The unbinned weighted histogram analysis method (UWHAM) is an implementation of the MBAR thermodynamic reweighting method for R. It is used in this tutorial to compute binding free energies from the output of SDM calculations. The UWHAM package is part of the CRAN archive. To install it do:

R
install.packages("UWHAM")

VMD

VMD is an indispensable tool for visualization and analysis of trajectories. Also, we use the catdcd tool distributed with VMD to parse and concatenate .dcd trajectory files. For this tutorial we will assume that VMD is installed in /usr/local.

Appendix

A. Installation of msys

The msys package provides the mae2dms utility to convert Maestro files into the DMS format.

We assume an Ubuntu 16.04 system and a Conda 2 environment. Below we assume the Conda environment is located in $HOME/miniconda2. Change it to match your environment:

source $HOME/miniconda2/bin/activate

msys's primary requirements are boost, scons and sqlite3:

sudo apt install libboost-dev libboost-all-dev
sudo apt install scons
sudo apt install sqlite3 libsqlite3-dev

Retrieve the msys sources from the DE Shaw Research github archive. In the commands below we assume this is done in the devel folder of the user home directory. Change it to match your build environment.

cd $HOME/devel
git clone https://github.com/DEShawResearch/msys.git

Consult the installation section of the README file that comes with msys if the steps below do not work for you

cd $HOME/devel/msys
export PYTHONPATH=$HOME/devel/msys/external:$PYTHONPATH
scons -j4
scons -j4 PYTHONVER=27 MSYS_BOOST_PYTHON_SUFFIX=-py

For this tutorial we assume that msys will be installed in $HOME/local. Change to match your choice.

scons -j4 PYTHONVER=27 MSYS_BOOST_PYTHON_SUFFIX=-py install PREFIX=$HOME/local

make sure that $HOME/local is in your search paths:

export PATH=$PATH:$HOME/local/bin
export LD_LIBRARY_PATH=$LD_LIBRARY_PATH:$HOME/local/lib
export PYTHONPATH=$PYTHONPATH:$HOME/local/lib/python

Test the installation

cd $HOME
dms-info $HOME/devel/msys/tests/smarts_tests/PC32699.mae
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