Python Mutation Free Energy Calculations using BioExcel Building Blocks (biobb)

Workflow Type: Python

Mutation Free Energy Calculations using BioExcel Building Blocks (biobb)

Based on the official pmx tutorial.

This tutorial aims to illustrate how to compute a fast-growth mutation free energy calculation, step by step, using the BioExcel Building Blocks library (biobb). The particular example used is the Staphylococcal nuclease protein (PDB code 1STN), a small, minimal protein, appropriate for a short tutorial.

The non-equilibrium free energy calculation protocol performs a fast alchemical transition in the direction WT->Mut and back Mut->WT. The two equilibrium trajectories needed for the tutorial, one for Wild Type (WT) and another for the Mutated (Mut) protein (Isoleucine 10 to Alanine -I10A-), have already been generated and are included in this example. We will name WT as stateA and Mut as stateB.

The tutorial calculates the free energy difference in the folded state of a protein. Starting from two 1ns-length independent equilibrium simulations (WT and mutant), snapshots are selected to start fast (50ps) transitions driving the system in the forward (WT to mutant) and reverse (mutant to WT) directions, and the work values required to perform these transitions are collected. With these values, Crooks Gaussian Intersection (CGI), Bennett Acceptance Ratio (BAR) and Jarzynski estimator methods are used to calculate the free energy difference between the two states.

Please note that for the sake of disk space this tutorial is using 1ns-length equilibrium trajectories, whereas in the original example the equilibrium trajectories used were obtained from 10ns-length simulations.

Copyright & Licensing

This software has been developed in the MMB group at the BSC & IRB for the European BioExcel, funded by the European Commission (EU H2020 823830, EU H2020 675728).

Licensed under the Apache License 2.0, see the file LICENSE for details.

Version History

Version 4 (latest) Created 31st Jul 2023 at 08:33 by Genís Bayarri

Fixed step4 bug (make_ndx syntax)

Frozen Version-4 14945d6

Version 3 Created 22nd Nov 2022 at 10:07 by Genís Bayarri

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Frozen Version-3 3a780f5

Version 2 Created 22nd Nov 2022 at 10:02 by Genís Bayarri

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Frozen Version-2 04010c6

Version 1 (earliest) Created 7th Apr 2022 at 11:32 by Genís Bayarri

Initial commit

Frozen Version-1 bd37263
help Creators and Submitter
Hospital, A., & Bayarri, G. (2023). Python Mutation Free Energy Calculations using BioExcel Building Blocks (biobb). WorkflowHub.

Views: 2234

Created: 7th Apr 2022 at 11:32

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