WT vs mutant protein-protein complex MD: should mutant be generated from WT docked complex or redock

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GROMACS version: 2026
GROMACS modification:No
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I am working on MD simulations of wild-type p53 and mutant p53 protein-protein complexes.

For the wild-type p53 system, I performed protein-protein docking using ClusPro with 8 different protein partners. From the selected WT p53-protein docked complexes, I have already run MD simulations.

Now I want to run the same MD workflow for mutant p53 complexes. My original plan was to introduce the p53 mutations, redock mutant p53 with the same 8 protein partners using ClusPro, and then run MD simulations.

However, ClusPro is currently not loading for me, even after checking browser, VPN, internet connection, and network diagnostics.

So I am considering two possible approaches:

  1. Redock both WT p53 and mutant p53 with the 8 protein partners using another docking server, such as HDOCK, and then rerun MD for both WT and mutant systems.
  2. Use the already selected WT p53-protein complexes generated by ClusPro, introduce the p53 mutations directly into those bound complexes, then perform energy minimization, equilibration, and production MD for the mutant complexes.

My main question is about comparability of the MD results.

Since my WT simulations were already performed using ClusPro-generated complexes, would using HDOCK only for mutant p53 introduce docking-method bias? Or would it be more appropriate to introduce the mutations directly into the existing WT ClusPro complexes and then compare WT vs mutant MD trajectories?

I aim to study how p53 mutations affect protein-protein interaction stability, interface contacts, and later pulling/umbrella sampling/PMF analysis.

Any suggestions on the more scientifically defensible workflow would be very helpful.