LSDMap

LSDMap package is used to compute Locally Scaled Diffusion Map. Typical usage is to call the "lsdmap" script:

lsdmap -f <configuration_file> -c <structure_file> -t <topology_file> <other_options>

or using MPI:

mpiexec -n <number_of_processors> lsdmap -f <configuration_file> -c <structure_file> -t <topology_file> <other_options>

A typical example of configuration file is ./examples/lsdmap/config.ini The structure file should contain all the configurations needed to compute LSDMap (e.g., a multi-model .gro file). After execution of the script, a .ev and a .eg file should have been generated containing the eigenvectors and eigenvalues, respectively.

See the paper W. Zheng, M. A. Rohrdanz, M. Maggioni and C. Clementi, J. Chem. Phys., 2011, 134, 144109 for more information on how LSDMap works.

Prerequisites

Before installing LSDMap package, make sure that you have the following packages installed:

• NumPy; version 1.4.1 or larger

• Scipy; version 0.10.0 or larger

• mpi4py; version 1.0 or larger

• cython; version 0.20 or later

If not already available, installing LSDMap will automatically install:

• MDTraj

• h5py

• dask

• cloudpickle

Version 2.6.x or 2.7.x of python should be used.

Installation

The Python Distutils are used to build and install LSDMap, so it is fairly simple to get things ready to go. Following are very simple instructions on how to proceed:

1. First, make sure that you have NumPy, SciPy, mpi4py and cython installed. If not, get them from http://numpy.scipy.org/, http://mpi4py.scipy.org/, http://cython.org/. Compile/install them.

2. From the main lsdmap distribution directory run this command (plus any extra flags, e.g., --prefix or --user to specify the installation directory):

    python setup.py install
   

After installation, make sure that the folder bin inside your installation directory is included in your PATH. It contains the executable "lsdmap" that is used to compute LSDMap. Tests can be run in the folder examples/lsdmap. This folder contains the structure file aladip_1000.gro which contains 1000 configurations of alanine dipeptide in vacuum and an example of configuration file (.ini) that should be used to compute LSDMap. To test the program, simply type in this folder:

lsdmap -f config.ini -c aladip_1000.gro -t aladip.gro

After execution, a file ".ev" and a file ".eg" must have been generated. They contain the eigenvectors and eigenvalues of the Fokker-Planck operator, respectively. In the file ".ev", the first column corresponds to the values of the first eigenvector (largest eigenvalue), the second column corresponds to the values of the second one, and so on. The first line corresponds to the values of the eigenvectors for the first configuration given in the structure file, the second line corresponds to the second configuration, and so on.

LSDMap can be computed using MPI using a command similar to:

mpiexec -n <number_of_processors> lsdmap -f <configuration_file> -c <structure_file> -t <topology_file>

For more information on lsdmap command, simply type:

lsdmap -h

DM-d-MD

DM-d-MD (Diffusion-Map directed Molecular Dynamics) is an adaptive sampling algorithm based on LSDMap. For an introduction to DM-d-MD, see the paper J.Preto and C. Clementi, Phys. Chem. Chem. Phys., 2014, 16, 19181-19191.

DM-d-MD jobs are run through python scripts. For examples, see the examples/dmdmd_ala12 and examples/dmdmd directories. Other examples, using AMBER as the MD engine as opposed to GROMACS, are available in the examples folder that comes with Extasy wrappers (https://bitbucket.org/claughton/wrappers)

Prerequisites

In order to use DM-d-MD, it is required that GROMACS has been correctly installed and that "grompp" and "mdrun" commands are working properly for a serial utilization. If not, please visit http://www.gromacs.org/. The ExTASY wrappers python library is also required (https://bitbucket.org/claughton/wrappers)

Testing

The Folder examples/dmdmd contains an example of DM-d-MD python script (rundmdmd.py) as well as files required to run GROMACS MD simulations for the photoactive yellow protein (PYP). DM-d-MD can be launched by executing the command:

python rundmdmd.py

within the specified folder. Note: it may be wise to issue the command:

    setenv GMX_MAXBACKUP -1

first.

Diffusion-Map Sampling

DMap Sampling (Diffusion Map Sampling) is our most recent adaptive sampling algorithm. It combines LSDMap and techniques from Umbrella Sampling, metadynamics to offer the best way of exploring configuration spaces of macromolecular systems and estimating their free energy landscapes.

DMap Sampling consists in conducting biased Molecular Dynamics simulations (MD) where the biased potential is a local estimate of the free energy of the system along Diffusion Map coordinates. Since DMap coordinates are associated with slow time scales of MD simulations, it becomes easier to explore a wider region of the configuration space without remaining in local minima. To run the biased MD, an appropriate modified version of GROMACS is needed. To install it, see the paragraph Installation below.

Installation

In order to use DMap sampling, one should meet the following requirements:

1. Installing the LSDMap package from the 'dmaps' branch, i.e., by first using:

   git checkout dmaps

then installing the lsdmap package using

python setup.py install

Note that this version of LSDMap requires a shared ".so" library of python. This library can be generated during the installation of python by using the option "--enable-shared" when configuring python:

./configure --enable-shared ...

2. Installing the modified (serial, simple precision) version of GROMACS. The package can be git-cloned using the following command:

   git clone git://git.code.sf.net/p/dmaps-gromacs/code dmaps-gromacs-code

   Note that the package contains a modified version of GROMACS 4.6.1. Once cloned, follow the following steps to install the package:

   a. Create the GROMACS Makefile. The modified version of GROMACS should be configured similarly to the standard version of GROMACS 4.6, with single precision and GPU and MPI options disabled. Please refer to http://www.gromacs.org/Documentation/Installation_Instructions_4.6 for more information on how to build GROMACS. A typical way of configuring our modified version of GROMACS could be the following once the installation directory has been git cloned:

   cd dmaps-gromacs-code mkdir cmake-build cd cmake-build cmake .. -DGMX_BUILD_OWN_FFTW=ON -DCMAKE_INSTALL_PREFIX=/path/to/local/directory -DGMX_GPU=OFF -DGMX_MPI=OFF

   Beware that the above commands is a simple example. Some machines may require additional options to have GROMACS work properly. Again, refer to the GROMACS webpage above for more information.

   b. Before installing GROMACS, link the DMap Sampling library to it. Before using make or make install, you should tell GROMACS that it should consider a library called libdms.so at the compilation. The library was created when the LSDMap package was installed. First, you should find the location of this particular library. If the installation of LSDMap went properly, the corresponding path should be /path/to/site-packages/lsdmap/dmaps/critical/libdms.so, where path/to/site-packages is the path to the python "site-packages" folder where LSDMap has been installed. Then, starting from the folder dmaps-gromacs-code that was git cloned earlier, you should edit the file src/kernel/CMakeLists.txt. At line 78 in this file, "path/to/libdms.so" in "set(LIBDMS path/to/libdms.so)" should be modified to correspond to the absolute path to the library "libdms.so" that you found.

   c. Compile GROMACS by typing (from the folder cmake-build that was created in step a):

   make install

Testing

To run Diffusion Map Sampling, use the following command from the examples/dmaps directory:

dmaps -f settings

As the job progresses, logging messages will be written to the console. If Diffusion Map Sampling finished correclty it should have created 3 folders, corresponding to the first three iterations of the DMap Sampling procedure (in the file settings, niters=3 by default), called iterX, where X is the number of the iteration.

To analyze the results of a particular iteration, go inside the corresponding "iter" folder. From there, you can use the script phipsi.sh which is located in the parent directory, by typing:

../phipsi.sh

This will compute collective variables that are commonly used to analyze results of the system tested here, alanine dipeptide. A bunch of python scripts are available in the folder examples/dmaps/scripts to plot specific figures. For example, the file examples/dmaps/scripts/plotfephipsi.py can be used to plot the free energy landscape as a a function of the coordinates phi and psi computed after running the script phipsi.sh. From the same "iter" folder, using:

python ../scripts/plotfephipsi.py

will plot the desired figure. Note that it requires the modules matplotlib and densplot to be installed on the local host. The former can be downloaded from http://matplotlib.org/, whereas the latter can be git cloned from https://github.com/jp43/densplot and installed the usual way using

python setup.py install