Mutation Free Energy (pmx, non-equilibrium TI)

Alchemical free energy of a point mutation with pmx and GROMACS, estimated by Crooks, BAR and Jarzynski.

by Temple Compute

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W-10 · Mutation Free Energy (pmx, non-equilibrium TI)

Alchemical free energy of a point mutation with pmx and GROMACS, estimated by Crooks, BAR and Jarzynski.

Domain: BioExcel Building Blocks

Overview

Computes a fast-growth non-equilibrium mutation free energy with GROMACS and pmx (default Staphylococcal nuclease, PDB 1STN, Ile10 to Ala). From wild-type (stateA) and mutant (stateB) equilibrium trajectories it builds hybrid structures and topologies, equilibrates, and runs one fast TI transition per direction. The final pmxanalyse estimate uses the precomputed dHdl bundles dhdlA_zip/dhdlB_zip (pmx tutorial, Ile10Ala), not this run's own transitions. The workflow has 23 tasks.

Pipeline

gmx_trjconv_str_ens_stateA / _stateB       Extract snapshots from each equilibrium trajectory
pmxmutate_stateA / _stateB                 Model mutated structures
pdb2gmx_stateA / _stateB                   Topology per state
pmxgentop_stateA / _stateB                 Hybrid dual-topology
make_ndx_stateB                            FREEZE index for stateB dummy atoms
grompp_min_stateB ──► mdrun_min_stateB ──► gmx_energy_min_stateB   Minimize dummy atoms
grompp_eq_stateA ──► mdrun_eq_stateA ──► gmx_energy_eq_stateA      NPT equilibration
grompp_eq_stateB ──► mdrun_eq_stateB ──► gmx_energy_eq_stateB      NPT equilibration
grompp_ti_stateA ──► mdrun_ti_stateA       Fast TI, WT to mutant
grompp_ti_stateB ──► mdrun_ti_stateB       Fast TI, mutant to WT
pmxanalyse                                 Free energy (CGI, BAR, Jarzynski)

Inputs / Outputs

Inputs: stateA and stateB .tpr/.xtc equilibrium runs and the dHdl bundles, all bundled in pmx_tutorial/.
Outputs (results/): mutA.pdb, mutB.pdb, pmxA_top.zip, pmxB_top.zip, eqoutA.gro, eqoutB.gro, tiA.gro, tiA_dhdl.xvg, tiB.gro, tiB_dhdl.xvg, pmx.txt, pmx.plots.png.

Parameters

| id | Default | Meaning | |---|---|---| | mutation_resnum | 10 | Residue number to mutate | | wt_residue | Ile | Residue in stateA (wild type) | | mut_residue | Ala | Residue in stateB (mutant) | | frame_interval_ps | 200 | Snapshot spacing in each 1 ns trajectory | | stateA_tpr, stateA_traj | pmx_tutorial/stateA.tpr, stateA_1ns.xtc | Wild-type equilibrium run | | stateB_tpr, stateB_traj | pmx_tutorial/stateB.tpr, stateB_1ns.xtc | Mutant equilibrium run | | dhdlA_zip, dhdlB_zip | pmx_tutorial/dhdlA.zip, dhdlB.zip | Precomputed dHdl work curves, WT to mutant and back |

The mutation must match the uploaded trajectories.