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[Licence| Download | New Version Template] aetq_v1_1.tar.gz(5255 Kbytes)
Manuscript Title: GMXPBSA 2.1: a GROMACS tool to perform MM/PBSA and computational alanine scanning
Authors: C. Paissoni, D. Spiliotopoulos, G. Musco, A. Spitaleri
Program title: GMXPBSA 2.1
Catalogue identifier: AETQ_v1_1
Distribution format: tar.gz
Journal reference: Comput. Phys. Commun. 186(2015)105
Programming language: Bash, Perl.
Computer: Any computer.
Operating system: Linux, Unix OS.
RAM: 2147483648 bytes
Supplementary material: A table of added keywords is available.
Keywords: Molecular dynamics simulation, Binding Free Energy, Virtual screening, GROMACS, Computational Alanine Scanning, MM/PBSA.
Classification: 3.

External routines: Any APBS version (http://www.poissonboltzmann.org/apbs/) and GROMACS version 4.5 or later installations (http://www.gromacs.org). Optionally LaTeX.

Does the new version supersede the previous version?: Yes

Nature of problem:
Calculates the Molecular Mechanics (MM) data (Lennard-Jones and Coulomb terms) and the solvation energy terms (polar and nonpolar terms respectively) from an ensemble of structures derived from GROMACS molecular dynamics simulation trajectory. These calculations are performed for each single component of the simulated complex, including protein and ligand. In order to cancel out artefacts an identical grid setup for each component, including complex, protein and ligand, is required. Performs statistical analysis on the extracted data and comparison with wild-type complex in the case of either computational alanine scanning or calculations on a set of simulations. Evaluates possible outliers in the frames extracted from the simulations during the binding free energy calculations.

Solution method:
The tool combines the freely available programs GROMACS and APBS to:
  1. extract frames from a single or multiple complex molecular dynamics (MD) simulation, allowing comparison between multiple trajectories;
  2. split the complex frames in the single components including complex, protein and ligand;
  3. calculate the Lennard-Jones and Coulomb energy values (MM terms);
  4. calculate the polar solvation energy values using the implicit solvation Poisson-Boltzmann model (PB);
  5. calculate the nonpolar solvation energy value based on the solvent accessible surface area (SASA);
  6. combine all the calculated terms into the final binding free energy value;
  7. repeat the same procedure from point 1 to 6 for each simulation in the case of computational alanine scanning (CAS) or simultaneous comparison of different Mds.

Reasons for new version:
We had a lot of feedback from our previous GMXPBSA 2.0 publication suggesting improvements. There were also some bugs that required to be fixed urgently in order to keep the program working properly.

Summary of revisions:
In the update version of GMXPBSA 2.1 we include the following changes:
  1. Fixed bug related to the use of amino acids with id > 1000.
  2. Fixed bug related to the computing of the percentage of failed APBS-jobs.
  3. Added the string 'export LC_NUMERIC="en_us.UTF-8"' in each of the three gmxpbsa*.sh scripts to avoid errors related to locale environment variables.
  4. Fixed a bug related to the CAS mutation in the cases in which:
    1. - no chains information is available from xtc/tpr
    2. - the ligand is positioned before the receptor in the pdb
  5. Added final message with proper references.
  6. Added the possibility of checking the GMXPBSA version with the command "sh gmxpbsa[0,1,2].sh -h ".
  7. Included the possibility to use "multichain". (Added keyword "multichain", set by default to "n"). Useful if in the pdbs extracted from the trajectory there is more than one chain. The option "multichain" must be used ONLY if the string TER is not present at the end of each chain in the comp/receptor pdb files.
  8. Added the possibility of performing ΔG CAS calculations on a single protein. Added keyword "protein_alone", set by default to "n", and keyword "itp_protein" that must be set only in the case of "use_topology=y". When using the option "protein_alone" in the xtc file provided to GMXPBSA the periodic boundary condition must be treated so as to make the broken molecules whole (i.e. trjconv -pbc whole).
  9. Modified default values for keywords: coulomb from "coul" to "gmx", precF from "1" to "0", linearized from "n" to "y".
  10. Added the possibility of using custom name of trajectories and binary file, xtc and tpr respectively format.
Many keywords have been added to allow more flexibility with the APBS options in the input file and to set the option for the cluster. See Table 1 of supplementary material for a list of all the added keywords.

Input format files compatible with GROMACS engine 4.5 and later versions. Availability of the force field or of the topology files.

Running time:
On a single core Lennard-Jones, Coulomb and nonpolar solvation terms calculations a require few minutes. The time required for polar solvation terms calculations depends on the system size.