Protein-Ligand System Preperation for Gromacs Simulations using LigParGen

  1.  Add the missing side chains using Modeller and can be done in Chimera, but you need to obtain key to access Modeller service online
  2. Clean the protein i.e, delete solvent and add missing side chains etc using Dock Prep in Chimera by running the following script. The script below also adds hydrogens to the ligand and saves it to ligand_wH.pdb file. Cleaned protein is saved to protein_clean.pdb
  3. Upload ligand_wH.pdb file to LigParGen server and download the zip file and unzip and keep the files in the same folder
  4. Make sure you installed Gromacs on your system
  5. Download OPLS-AA/M protein force field parameters from JorgensenResearch Group page and save it to your Gromacs topology folder.
  6. Run the following python script

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Protein-Ligand System Preperation for Gromacs Simulations using LigParGen

Protein-Ligand System Preparation for NAMD simulations with VMD/LigParGen

      1.  Add the missing side chains using Modeller and can be done in Chimera, but you need to obtain key to access Modeller service online
      2. Clean the protein i.e, delete solvent and add missing side chains etc using Dock Prep in Chimera by running the following script. The script below also adds hydrogens to the ligand and saves it to ligand_wH.pdb file. Cleaned protein is saved to protein_clean.pdb
      3. Upload ligand_wH.pdb file to LigParGen server and download the zip file and unzip and keep the files in the same folder
      4. Download OPLS-AA/M protein force field parameters from Jorgensen Group Research page and save it to the same folder
      5. Run the following Tcl script with VMD to create psf and pdb files needed to run NAMD simulations

 

 

Protein-Ligand System Preparation for NAMD simulations with VMD/LigParGen

How to Install LigParGen Server Locally ?

I have many received many requests about making a local version of LigParGen server so that one doesn’t have to upload their ligand files to the web server. So we have made LigParGen python package that can be installed on Linux & Mac machines with anaconda python. Please follow the below steps to have a local version of LigParGen

  1. Install anaconda python
  2. Please request BOSS executable from Prof. William L. Jorgensen (It is free for academic users). Once you have BOSS, set $BOSSdir
  3. type `conda install -c mc-robinson ligpargen openbabel ` to install the package
  4. Download the files from here and copy them to $BOSSdir/scripts folder
  5. If this is done type “Converter -s ‘c1ccccc1’ -r BNZ -c 0 -o 0 -l” ,  this should generate BNZ.* in your tmp file. These are topology and parameters for Benzene in different force field formats.

Please email me if you have any questions at leela.dodda@yale.edu

Acknowledgements: Thank you, Matthew Robinson !! for Packaging LigParGen scripts.

Hope this makes your simulation setup a whole lot easier.

How to Install LigParGen Server Locally ?

LigParGen Server: An automatic OPLS-AA parameter generator for organic ligands

LigParGen is a web service offered by Prof. William L. Jorgensen’s research group. As part of the team that developed this service, I am happy to announce the availability of LigParGen server to general use. I hope this will be useful for you all. Any feedback or comments are highly appreciated.  Details about the server are given below.

ligpargen

jorgensenresearch.com/ligpargen

Condensed phase simulations of organic and biomolecular systems have become a common practice these days to explain experimental observations and measurements.   To perform an  condensed phase simulations accurately, one need a good force field to represent the system. Some of the commonly used force fields are OPLS-AA, AMBER, CHARMM . OPLS-AA force field stands for Optimized Potentials for Liquid Simulations, in particular, is parameterized to reproduce experimental pure liquid properties such as densities, heats of vaporization. Given the magnitude of chemical space, it is impossible to get charges and parameters for every molecule. So a generalized OPLS-AA force field parameter set for different atoms types was created and charges are obtained using CM1A charge model (that is based on semi-empirical AM1 calculation), and these gas phase charges are scaled to account for condensed phase polarization. These charge models are parameterized to reproduce pure liquid properties and free energies of hydration

LigParGen is a free web service that provides OPLS-AA intra- and inter-molecular parameters needed to run  molecular simulations. It accepts both 3D : PDB, MOL and 2D : SMILES files. One can also use draw molecule functionality and submit the molecule. This server provides parameters not just for neutral molecules but also for ions from charge ranging from +2 to -2. User can also choose to optimize the input structure or just perform single point calculation. This request will be processed by BOSS package, which then calculates CM1A charges using AM1 functionality.

Once the request is successfully processed, user will be redirected to a page with JSME tool to visualize the structures, necessary parameter and topology files to run MD simulations with commonly used MD packages such OpenMM, Gromacs, NAMD and CHARMM and a publication quality image of the ligand. The user can choose to download a chosen file or zip file with all the above-mentioned files.

This website also provides detailed tutorials on how to run protein-ligand simulations using NAMD and Gromacs using the parameter and topology files from the server.

LigParGen Server: An automatic OPLS-AA parameter generator for organic ligands

Energy component analysis for OpenMM

OpenMM has been gaining popularity because of the flexibility it offers for scientists to implement new methodologies and force fields. But it is still not straightforward enough to give you the energy contributions from each component of force-field. Thanks to the developers of Parmed package,  it easy for the fan base of other MD packages to now shift to OpenMM. This package also provides a smooth access to energy component analysis.

In this blog post I include code to do energy component analysis for   a molecule like Aniline using Parmed-OpenMM combo. Here are the structure and forcefield files. Output is also shown in the gist. Hope this will make your life easier when implementing new force-fields.

Energy component analysis for OpenMM