SilcsBio Software Installation¶

Minimum hardware requirement¶

SilcsBio software requires relatively robust computational resources for the molecular dynamics (MD) components of the SILCS and SSFEP protocols. For example, computing SILCS FragMaps for a 35 kDa target protein takes 80-90 hours of walltime when run in parallel on ten compute nodes, each equipped with 8 3-GHz CPU cores. The software can take advantage of GPU acceleration: the addition of a single NVIDIA GeForce RTX 2070 GPU to each node will reduce the walltime to 24-48 hours. In the case of SSFEP, walltime using these GPU-equipped nodes will be 3-4 hours.

SilcsBio software is designed to run the compute-intensive MD on a cluster using a cluster queue management system such as OpenPBS, Sun Grid Engine, or SLURM. With both SILCS and SSFEP, subsequent evaluation of relative ligand affinities takes seconds to minutes on a single CPU core, allowing for modifications to be rapidly evaluated for a large number of ligands to a given target.

For customers without ready access to an appropriate in-house computing cluster, SilcsBio offers three possible solutions. The first solution is the SilcsBio Workstation. The SilcsBio Workstation combines the SilcsBio server and GUI software with high-performance GPU-computing hardware in a quiet, sleek form factor for use in an office setting. The SilcsBio Workstation is a complete turn-key solution that is ready to plug in to a standard wall electrical socket. The second solution is for SilcsBio to perform computations as a service and supply data to the customer for subsequent in-house analysis. For this service, in the case of SILCS, SilcsBio requires only the structure of the target, and, in the case of SSFEP, only the structure of the protein-parent ligand complex. Depending on the choice of SSFEP or SILCS, no intellectual property disclosure to SilcsBio in the form of proposed chemical modifications to the parent ligand (SSFEP) or even the parent ligand itself (SILCS) is required. The third solution is for SilcsBio to assist customers with setting up their own virtual cluster using Amazon Web Services. Please contact info@silcsbio.com for additional information on these solutions.

Python 3 requirement¶

The SilcsBio server software requires a working Python 3 installation. We recommend using Miniconda (https://docs.conda.io/en/latest/miniconda.html) for installing Python 3. Once Python 3 is installed, you will need to install some additional Python packages. To do so, run the following command:

pip install -r $SILCSBIODIR/utils/python/requirements.txt

GROMACS requirement¶

Both SILCS and SSFEP molecular dynamics simulations require the GROMACS molecular dynamics software. We recommend GROMACS version 2021.4. GROMACS can be obtained at https://manual.gromacs.org/documentation/2021.4/download.html and must be installed in order to use the SilcsBio software package.

We strongly recommend building GROMACS with GPU acceleration enabled. Below is a sequence of commands for GROMACS v. 2021.4 installation with GPU acceleration:

cd <GROMACS source directory>
mkdir build
cd build
cmake .. -DGMX_BUILD_OWN_FFTW=on \
  -DREGRESSIONTEST_DOWNLOAD=on \
  -DGMX_GPU=CUDA \
  -DGMXAPI=off \
  -DBUILD_SHARED_LIBS=off \
  -DGMX_PREFER_STATIC_LIBS=on \
  -DGMX_BUILD_SHARED_EXE=off \
  -DCMAKE_INSTALL_PREFIX=<GROMACS install location>
make
make install

If your compute nodes do not have GPUs, use the following commands:

cd <GROMACS source directory>
mkdir build
cd build
cmake .. -DGMX_BUILD_OWN_FFTW=on \
  -DREGRESSIONTEST_DOWNLOAD=on \
  -DGMXAPI=off \
  -DBUILD_SHARED_LIBS=off \
  -DGMX_PREFER_STATIC_LIBS=on \
  -DGMX_BUILD_SHARED_EXE=off \
  -DCMAKE_INSTALL_PREFIX=<GROMACS install location>
make
make install

Please refer to http://manual.gromacs.org/documentation/current/install-guide/index.html for further details.

Installing the SilcsBio server software¶

The SilcsBio server software package is delivered as a zip-compressed file. Unzip and place the files to an accessible location. The files have the following directory structure

silcsbio.$VERSION/
  data/
  examples/
  lib/
  programs/
  silcs/
  silcs-hotspots/
  silcs-mc/
  silcs-memb/
  silcs-pharm/
  ssfep/
  ssfep-memb/
  templates/
  utils/
  VERSION

The top-level silcsbio.$VERSION/ folder contains software for running SILCS and SSFEP simulations. The programs/, silcs*/, and ssfep*/ folders contain executable code, and the templates/ folder contains templates for job handling and input scripts. Some template files may need to be edited with information for your queuing system.

If you are a system administrator, place the top-level silcsbio.$VERSION/ folder where it can be accessed by other users, such as /opt/silcsbio/. If you are a single user, you may place the folder in your home directory.

For SilcsBio server software to work, the two shell environment variables GMXDIR and SILCSBIODIR need to be set. To do so, replace <gromacs/bin> and <silcsbio> with the complete file paths for the corresponding folders:

# bash
export GMXDIR=<gromacs/bin>
export SILCSBIODIR=<silcsbio>

Currently, the SilcsBio server software is compatible only with the Bash shell environment. You may insert the above environment variable settings in .bashrc for convenience.

Installing the SilcsBio Graphical User Interface¶

The SilcsBio Graphical User Interface (GUI) enables running SILCS and SSFEP simulations and analyzing results through a GUI instead of the command line. The SilcsBio GUI is available for Windows, macOS, and Linux. Please download and install the software on your local desktop or laptop computer.

In addition to providing standalone features such as FragMap visualization and ligand modification, the SilcsBio GUI can set up, launch, manage, and analyze compute-intensive SILCS and SSFEP simulations. To enable this functionality requires a simple configuration step to allow the GUI to communicate with your SilcsBio server software.

Please follow the Remote server setup process as described in Graphical User Interface Quickstart. Contact support@silcsbio.com if you need help with this process.