Protein helices in rainbow colours around a bound lipid substrate shown as spheres

CompBioChem Tutorials QM/MM

Tutorial for Transition State (TS) searches of Enzymatic Reaction Mechanisms using QM/MM methods in CP2K

Locate the reactant, transition state and product of an enzymatic reaction with QM/MM geometry optimizations, a potential energy surface scan, the CI-NEB method, vibrational analysis and the dimer method in CP2K.

Start with Section I Source on GitHub
  • Part 2 of Enzyme QM/MM with CP2K
  • CP2K
  • parmed

Alexandre V. Pinto, PhD in Chemistry

High Performance Computing in Molecular Modelling Research Group, LAQV-REQUIMTE

Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto


This tutorial aims to characterize, using a QM/MM methodology, the reactant, transition state and product geometries found with the climbing image nudged elastic band (CI-NEB) and the dimer methods along a given reaction path.

It requires the *prmtop and *rst7 files of a solvated protein-ligand complex parameterized with an Amber force field, previously equilibrated with MD simulations in the intended ensemble, and PBC corrected. The *prmtop file and the &QMMM section of the CP2K input should be prepared according to the tutorial QMMM for biochemical systems. You need to use parmed to produce an additional *prmtop file where the charges of the QM/MM link have been corrected, considering that the MM charges of the QM region will be removed in the electrostatic embedding scheme. The QM selection should be prepared carefully, considering the demands in terms of accuracy* brought forward by the reaction in question, and in terms of calculation speed brought forward by the available computational resources. You should also follow the good practices found in the literature, other tutorials, discussion groups,... in fact most of the information present in this tutorial came from the CP2K site, the CP2K manual and the CP2K discussion group. This method has been employed in the Revisiting the reaction pathways for phospholipid hydrolysis catalyzed by phospholipase A2 with QM/MM methods paper. See the bottom of this page for other useful resources.

Once these requirements are fulfilled, you are ready to start this tutorial.

*Note that the QM method in the provided inputs is the semiempirical SCC-DFTB with D3(0) dispersion correction, which allows for considerably fast calculations but has several limitations. The strategy suggested here is to get a good TS guess with SCC-DFTB-D3(0) and then refine the results with a more accurate level of theory.