QligFEP v2.0 and QresFEP v2.0

This collection of python command line functions is designed with the aim to faciliate a robust and fast setup of FEP calculations for the software package Q. These modules use python 3, python 2 is no longer supported, and an old version of the code using python 2 is now only available in the python2 branch.

This pacakge includes at the moment four main modules:

• QligFEP.py: module to generate ligand FEP calculations using a dual topology approach, see Jespers et al. (https://doi.org/10.1186/s13321-019-0348-5).

• QresFEP.py: module to generate protein FEP calculations using either a single topology approach, see Jespers et al. (https://doi.org/10.1021/acs.jctc.9b00538), or using a dual topology approach, see Koenekoop et al. (https://doi.org/10.1038/s42004-025-01771-0).

• QLIE.py: module to generate ligand LIE calculations.

Future versions will include several translation tools for new forcefields (at the moment we support opls, charmm, amber and openFF).

A few toplevel scripts are included in the scripts folder to faciliate high throughput setup. Additionally, a tutorials folder is included, with one tutorial showing a detailed description of the setup procedure for ligand mutations as published in Jespers et al. (QligFEP). This tutorial includes the generation of ligand parameters using OPLS, how to prepare a protein system, and how to run ligand FEP calculations. These examples are based on ligand binding of CDK2 inhibitors. Another tutorial shows a detailed description of the setup procedure for residue mutations as published in Koenekoop et al. (QresFEP). This tutorial includes the generation of mutant amino acids, how to prepare a protein system, and how to run residue FEP calculations. These examples are based on thermal stability shifts of T4L mutants.

Installing QligFEP and QresFEP

• Install a working version of Q, e.g.: https://github.com/esguerra/Q6

• Clone this repository:

    git clone https://github.com/qusers/qligfep.git
  

• Initialize the repository:

    bash qligfep_init.sh
  

  This will add qligfep repo executables to your $PATH and update the settings.py script with:

  • Q_PATH: the path to your Q installation
  • SCHROD: the path to your Schrödinger installation
  • DEFAULT: your working HPC cluster (or localhost)

  You can modify you setting.py script further manually to add more clusters or cluster options.

Requirements

Schrödinger

• PyMOL
• Protein Preparation Wizard
• ffld_server

Software

• Q
• cgenff
• Python3.XX

Python packages

• mdtraj

contact: [email protected]