Welcome to the documentation for transformato!

The python package transformato (Tool Running MD AgNoStic Calculations FOR Multistate Serial ATOm Insertion) is an implementation of the Common Core / Serial-Atom-Insertion (CC-SAI) approach [1] for calculating free energy differences. It does so by connecting the physical endstates of two molecules via alchemical pathways.

It requires very little set-up time and is designed to work directly with output from CHARMM - GUI. Currently either relative solvation free energies (RSFE) [2] or relative binding free energies (RBFE) [3] can be calculated. For the production runs either CHARMM or openMM are required.

If you’d like to take a look at the code, head over to our github repository.

Contents:

• Theoretical background
  • Interplay with CHARMM-GUI
  • The common-core approach
  • Serial-Atom-Insertion approach
  • Citations, License and Contact
  • Acknowledgements
• Installation
  • Prerequisites
  • Getting \(\texttt{TRANSFORMATO}\)
• System Setup
  • Step 1 – creating Systems using CHARMM-GUI
  • Step 2 – modifying the yaml file
• Additional Settings
  • Restraints
  • Hydrogen Mass Repartitioning (HMR)
• Running Simulations
  • Step 3 - Creating intermediary states
• Trajectory Analysis
  • The analysis.py file
  • Offloading the analysis to a cluster
• Troubleshooting
  • Getting debug information
  • Error messages and common causes:
• API Documentation

References

[1]

Boresch, S., Bruckner, S. (2011). Avoiding the van der Waals endpoint problem using serial atomic insertion J.Comput. Chem. 2011,32, 2449–2458, DOI ⤶

[2]

Wieder, M., Fleck, M., Braunsfeld, B., and Boresch, S. (2022). Alchemical free energy simulations without speed limits. A generic framework to calculate free energy differences independent of the underlying molecular dynamics program. J. Comput. Chem. 43, 1151–1160, DOI ⤶

[3]

Karwounopoulos, J., Wieder, M., and Boresch, S. (2022). Relative binding free energy calculations with Transformato: a molecular dynamics engine-independent tool. Front. Mol. Biosic. 9:954638, DOI ⤶

Maintainers

• Markus Wieder, Department of Pharmaceutical Sciences, University of Vienna

• Johannes Karwounopoulos, Institute of Computational Biological Chemistry, University of Vienna

• Stefan Boresch, Institute of Computational Biological Chemistry, University of Vienna

• Index