README

This is a repository for the CABSdock standalone application for molecular docking of peptides to proteins. CABSdock allows for flexible docking (also with large-scale conformational changes) without knowledge about the binding site. CABSdock enables peptide docking using only information about the peptide sequence and the protein receptor structure. Many advanced options are available that allow for manipulation of a simulation setup, the degree of protein flexibility or guiding the peptide binding etc.

Detailed instructions and tutorials are provided on CABSdock WIKI PAGE

CABSdock can be installed on Linux, macOS or Windows. To install follow these steps:

1. Install Python2.7

Linux

Most Linux distributions come with Python2.7 already installed. To check if you have the correct Python version open the terminal and type:

python --version

macOS

macOS comes with Python2.7 already installed. To check if you have the correct Python version open the Terminal.app and type:

python --version

If you get the message: bash: python: command not found it may mean that your system doesn't have Python installed, or Python's binary is not in the system PATH. To check this run in the Terminal.app the following command:

/Library/Frameworks/Python.framework/Versions/2.7/bin/python --version

If you still get the message: bash: python: command not found you need to install Python2.7. Otherwise add Python's binary to the system's PATH by running in the Terminal.app the following command:

echo "export PATH=/Library/Frameworks/Python.framework/Versions/2.7/bin/:$PATH" >> ~/.bash_profile

Windows

Follow instructions on python.org. To check if you have the correct Python version open command prompt (press cmd + R; enter "cmd"; hit enter) and run the following command:

python --version

If you get the message: python: command not found add Python's binary to the system's PATH by running in the command prompt the following command:

set %PATH% = %PATH%;"C:\\path\\to\\python\\binary"

Minimum required python version for CABSdock is 2.7.12. You can always download latest version from python.org. Note that Python3.X is NOT the latest version of Python2.7 and you should always use Python2.7 to run CABSdock.

###2. Install pip

Linux / macOS / Windows

Assuming you've already installed Python2.7 and made it accessible under command "python", download this script, change to the directory with downloaded script and run:

python get-pip.py

###3. Install CABS

Linux / macOS / Windows

Download latest CABS package from https://bitbucket.org/lcbio/cabsdock/downloads and run:

pip install CABS<version>.tar.gz

If you get an error during installation of the matplotlib regarding missing libpng and/or libfreetype libraries you need to install them prior to installing CABS. These should normally be already present on your system.

###4. Install gfortran

Follow instructions on https://gcc.gnu.org/wiki/GFortran

###5. Install MODELLER (optional) Follow instructions. Remeber to add /modeller/installation/directory/modlib to PYTHONPATH system variable.

CABSdock uses some external software packages for the following tasks:

• gfortran - Fortran compiler for the CABS core simulations subroutines.
• MODELLER - program for modeling of protein structure using spatial restraints. CABSdock uses MODELLER for the reconstruction of predicted complexes from tha C-alpha to all-atom representation.
• libpng - library for the png bitmaps.
• libfreetype - library for the freetype fonts.

ABOUT THE METHOD

CABSdock method has been first made available as a web server. The standalone application version [submitted to publication] provides the same modeling methodology equipped with many additional features and customizable options.

The following papers describe the CABS-dock method/ web server/ and its example applications:

• CABS-dock web server for flexible docking of peptides to proteins without prior knowledge of the binding site, Nucleic Acids Research, 43(W1): W419-W424, 2015
• Modeling of protein-peptide interactions using the CABS-dock web server for binding site search and flexible docking, Methods, 93, 72-83, 2016
• Protein-peptide molecular docking with large-scale conformational changes: the p53-MDM2 interaction, Scientific Reports 6, 37532, 2016
• Highly flexible protein-peptide docking using CABS-dock, Methods in Molecular Biology, 1561: 69-94, 2017

CABS-dock pipeline consist of the three following modules:

• Simulation module – performs docking simulations using peptide sequence, protein structure and set of parameters as the input. With default settings the module outputs a set of 10’000 of models (10 trajectories consisting of 1000 models) in C-alpha representation.
• Scoring module – selects representative and best-scored models from the simulation module output. Scoring module outputs sets of 10, 100 and 1000 top-scored models in C-alpha representation.
• Reconstruction to all-atom representation module – uses a Modeller package to reconstruct a set of 10 top-scored models from C-alpha to all-atom representation.

Laboratory of Computational Biology, 2017