akosny / mdfit

Automated molecular dynamics simulations workflow for high-throughput assessment of protein-ligand dynamics

MDFit

Python wrapper for high-throughput molecular dynamics. A workflow overview and application of MDFit to a data set of macrocyclic peptides targetting PD-L1 are discussed in TBD.¹

MDFit currently uses Schrodinger tools. Implementation of alternatives, including open-source tools, are ongoing.

Prerequisites

MDFit assumes the $SCHRODINGER environmental variable has been set. This should point to the current Schrodinger installation. To check if $SCHRODINGER has been set correctly, try running: $SCHRODINGER/run -h

MDFit attempts to get the current Schrodinger release by reading the $SCHRODINGER pathname. For example, if the current release is installed in /schrodinger/2023-2/, MDFit will set the release to 2023-2. This value can also be hard-coded in MDFit (line 38) if a different directory naming scheme is used.

The first time MDFit.py is called, a parameters_TEMPLATE.json file is generated in the installation directory. Replace localhost with your institution's Schrodinger hostnames and rename the file to parameters.json. This is required only once and MDFit will always read parameters.json to get host information on subsequent runs. General runtime limit guidance:

FFBUILDER   10 hours
BMIN        2 hours
MULTISIM    2 hours
DESMOND     24 hours
ANALYSIS    8 hours

Usage

$SCHRODINGER/run python3 MDFit.py -h

Self-contained example available in MDFit/Examples/PDL1/. The following command will run FFBuilder, three repetitions of 100 ns Desmond MD, and MD analysis for Pep-01, Pep-41, Pep-52, and Pep-66. The first 100 frames will be removed from the trajectory before analysis (--slice_start) and the cutoff for retaining a protein-ligand interaction is 0.3 (--analysis_cutoff).

$SCHRODINGER/run python3 MDFit.py -p 6PV9_PDL1.mae -l MDFit_PDL1_Example_Ligands.mae -o "MDFit/Examples/PDL1/PDL1_oplsdir" -t 100000 -r 3 --slice_start 100 --analysis_cutoff 0.3 -d

It is strongly encouraged to use the debug flag -d for initial MDFit usage. Errors may occur if packages are not where MDFit expects them to be.

Bugs and Known Errors

• Schrodinger release relying on installation pathname.

Footnotes

1. Reference TBD ↩