Is it useful to energy minimize a docked pose before scoring it? I am speaking in the context of protein-ligand systems. Does the energy obtained after minimization correlate better with experimental affinity?
Does someone have some published literature on that?


2 Answers 2


One way these calculations are performed is using MD and implicit solvent calculations. The general procedure for these simulations are:

  1. Perform simulations and get frames

  2. Perform implicit solvent calculations on the complex, receptor, and ligand

  3. Calculate docking energy from the three individual components

Generally there is not an additional minimization that is performed as it could bias the sampling to a particular energy well. This would mean you could lose out on valuable information, such as why a pose is not favorable.


Absolutely not.

You only need that your input structure geometry is ok (no atomic clash, all valence ok, etc ).

Using DFT or Molecular Dynamics to optimize the geometry pre docking is a waste of time.

The justification to that is that every docking software will generate/search for a population of conformers, so, each conformer will be out of optimal geometry.

  • $\begingroup$ Maybe ma question needs to be clarified, I am talking about minimization of the complex after docking and then scoring, not minimizing the geometry before docking. $\endgroup$
    – BND
    Commented Jun 18, 2020 at 15:58
  • $\begingroup$ Oh, I got it. Well, the answer is no. The molecular docking is, per se, an individual methodology, so after having your poses, you don't need to do anything else. BUT, you can use other simulations methods (MD, FMO, etc.) in order to validate your docking results. $\endgroup$
    – Camps
    Commented Jun 18, 2020 at 16:14
  • $\begingroup$ Any advice on an accessible FMO or FEP tool. $\endgroup$
    – BND
    Commented Jun 19, 2020 at 6:59
  • 1
    $\begingroup$ A software that can calculate FMO is GAMESS, but the trick here is to prepare the input. I tried to use FACIO, FU and FRAGIT, unsuccessfully. Here are the links. GAMESS: msg.chem.iastate.edu/gamess; FACIO: zzzfelis.sakura.ne.jp; FU: staff.aist.go.jp/d.g.fedorov/fmo/main.html and FRAGIT: github.com/FragIt/fragit-main. $\endgroup$
    – Camps
    Commented Jun 22, 2020 at 18:25

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